Neuroscience Tutorial

An illustrated guide to the essential basics of clinical neuroscience.

Neuroscience is on the frontier of human medical knowledge. The study of neurochemistry, the nervous system, and the brain all closely affect human thought, behavior, and emotion – and what’s more important than that?

This tutorial will guide you through some core concepts in neuroscience, including:

  • Coronal and Horizontal Sections
  • Basic Visual Pathway
  • Basic Somatosensory Pathway
  • Basic Motor Pathway
  • Eye and Retina
  • Central Visual Pathways
  • Auditory and Vestibular Systems
  • Somatosensory Pathways From the Body
  • Somatosensory Pathways From the Face
  • Spinal Motor Structures
  • Brainstem Nuclei of Cranial Nerves
  • Basal Ganglia and Cerebellum
  • Hypothalamus and autonomic Nervous System
  • Medial Temporal Lobe and Memory
  • Sleep and Language

Coronal and Horizontal Sections

A. Coronal Sections

Before you can appreciate sections through the brain, you need to know the planes of orientation. There are three types of sections: coronal, horizontal, and sagittal. They are diagrammed below.

Coronal sections are the easiest to visualize, because their orientation is just like looking face-on at another person. Up is up and down is down. We will start with the most rostral sections, or those closest to the nose.

Note: these sections have not been cut on a perfectly coronal plane, and are in fact tilted backwards a little. They will differ slightly from the pictures found in the DeArmond atlas. However, the relationships between structures are unchanged.

The very first section you would see in a coronal series would be just the tips of the frontal lobes, which sit right behind the forehead. We have skipped forward a little to the first section containing internal structures. These slides have been stained for myelin, which makes all of the white matter (axons) black. The grey matter (cell bodies) appears white. Paradox? The grey and white matter were originally named for their appearance in freshly cut brain tissue. Myelinated axons, with their high fatty content, look whiter than cell bodies.

The first thing to notice is the corpus callosum. This major highway connecting the two hemispheres will serve as a useful landmark, because it appears in all coronal sections. The color of the corpus callosum will also tell you the color of white matter, which can vary with the type of stain. In these sections, white matter is black. 

Below the corpus callosum you can see the tips of the two lateral ventricles. They are separated by a thin septum which carries a second set of axons, the fornix. The fornix is carrying information from the hippocampi to the mamillary bodies, and travels along the midline from back to front. It does not cross the midline like the corpus callosum, however. 


Notice the lumps of grey matter sitting in the lateral ventricles. These are the caudate nuclei, and the rule for identifying them is simple: if you can see lateral ventricles, you can see caudate. This applies throughout the curved extent of the lateral ventricles – the caudate follows them the whole way.

The caudate appears to blend into another nucleus (a nucleus is any collection of cell bodies), the putamen. These two nuclei are almost always divided by a band of axons called the internal capsule. But here in the rostral brain, you can see that the two are continuous at their bases. In reality, the caudate and the putamen are all one nucleus, which was coincidentally cut in half by the internal capsule. Early anatomists didn't realize this, so they were named separately, and the small bridge which connects them ventromedially was named the nucleus accumbens. All three nuclei are sometimes collectively called the striatum, however, to acknowledge their continuity.

You can also see the beginnings of a dark nucleus medial to the putamen. This nucleus has a lot of axons in it, so in fresh-cut brain it appears very pale. Hence it is named the globus pallidus.

In the next most caudal section, some things have changed. Notice that the nucleus accumbens is gone and the caudate and putamen are no longer connected. There is also a moustache-like tract crossing from right to left. This is the anterior commissure, and represents one of only two major tracts that connect the hemispheres. The other is the corpus callosum. The posterior commissure, which connects the left and right midbrain, is small and hard to find.

In the next section, we see the arrival of another major player, the thalamus. The thalamus is really a heterogeneous group of nuclei, but they all share the same basic function – they are the gatekeeper for anything that wants to get up to cortex. The thalamic nuclei are located on either side of the slit-like third ventricle. This gives us another rule: if you can see third ventricle, you can see thalamus. Sometimes the thalamus will send a little bridge across the third ventricle, appearing to create two smaller ventricles. This is a normal anatomic variant. Notice that the thalamus sits on top of the internal capsule, while the putamen and globus pallidus remain below - this relationship is always preserved.


Speaking of the globus pallidus, in this section it begins to look like two nuclei. The outer shell is now called the globus pallidus externa, while the inner wedge is the globus pallidus interna.

The optic chiasm is visible here, hanging down below the base of the brain. It will split to form the optic tracts, which will burrow up into the brain. These pathways are carrying all of the information from the eyes. 


In the next section, the globus pallidus and putamen are beginning to recede, and the thalamus is increasing in size. The optic tracts are entering the brain. A new structure visible here is the amygdala. The amygdala is one of two major structures which are found on the medial surface of the temporal lobe (the other is the hippocampus). The amygdala has a characteristic marbled appearance in these sections, due to the axons winding through it. It is part of the limbic system, and deals with the emotional significance of experiences.

This is the last section of this series, and a lot has changed. The lateral ventricle is visible in two places. The lateral ventricle, like many other structures in the brain, curves back and loops under itself like a big C. Therefore, in some parts of the brain you can cut it in two places. The caudate follows this curve, so it can also be seen in two places.

The hippocampus has taken the place of the amygdala. The hippocampus, which looks distinctly like a jellyroll, is involved in memory formation and will be the subject of later sections.

In the center of this section, things look radically different. We are at the junction of brainstem and cerebrum, which is called the midbrain. The midbrain can be identified by two major landmarks: the cerebral aqueduct, which is the narrow channel between the third and fourth ventricles, and the cerebral peduncles. The cerebral peduncles are really a continuation of the internal capsule – move back one section and notice how it begins to stream down towards the base of the brain. The peduncles are quite literally the "stalk" of the cerebrum, and all of the axons passing up to or down from the brain are carried in them.


Just lateral to the peduncles are a pair of structures involved in vision, the lateral geniculate nuclei. They have a typical layered, peaked shape, and are the target of the optic tract. Right above the peduncles you can see the pale substantia nigra. The substantia nigra produces dopamine, and is critical for normal movement; Parkinson's disease is the degeneration of this nucleus. A byproduct of the production of dopamine, neuromelanin, accumulates with age and makes it look dark in fresh-brain preparations. This explains the name substantia nigra ("black stuff").

Above the substantia nigra are two perfectly round circles. These are the red nuclei (you guessed it, due to their appearance in fresh brain), which are involved with the cerebellum. They are another landmark of the midbrain, and the trio of peduncles, substantia nigra, and red nuclei are almost always found together.

Finally, we have the remains of the thalamus. This caudal-most extension of thalamus hangs over the midbrain and is called the pulvinar.

B. Horizontal Sections

Horizontal sections are often used clinically, as MRI and CT scans are taken in the horizontal plane. In these horizontal sections we will start at the top of the brain and cut sections downward. In the pictures, rostral (the nose) is up.

 Due to the unique curvatures of the brain, the relative locations of nuclei in horizontal cuts are strikingly similar to what you saw in coronal sections. For example, in this section, lateral ventricles can be found just under the corpus callosum, caudate can be found in the lateral ventricles, and putamen is separated from caudate by the internal capsule. There are some noticeable differences, however. First, you can see the full extent of the lateral ventricles, front to back. Second, you can see a large posterior fiber tract crossing from right to left. The posterior commissure? No, too big. This is part of the corpus callosum. The corpus callosum is U-shaped in cross section, but from the side it also curves like a C. In horizontal section, we cut through it twice. Third, the true shape of the internal capsule is revealed in horizontal section – it is V-shaped. It has an anterior limb and a posterior limb; the latter carries most of the pathways we will learn about later. 

Both thalamus and fornix are visible here, and since they make the walls and the roof of the third ventricle, respectively, we must be about to cut through third ventricle. 

In the next section we can indeed see the third ventricle and the thalamic nuclei on either side. The channel between the lateral ventricles and the third ventricle is visible, the foramen of Monro. The globus pallidus has appeared just where it should, nestled inside the putamen. We are beginning to lose the rostral part of the corpus callosum. The thalamus is very large in this section.

 In this last section we have cut all the way down to the midbrain. The midbrain appears upside down; remember that the peduncles are pointing towards your throat, so they will point down in coronal section but up in a horizontal section. Otherwise, all of the midbrain landmarks look pretty similar; you can see peduncles, substantia nigra, and red nuclei, along with the lateral geniculate (LGN) and its partner, the medial geniculate (MGN). The MGN is part of the auditory pathway, while the LGN is visual. The cerebellum, which sits at the back of the brain and coordinates movement, has been barely nicked in this section.

 Now that you are familiar with the major structures and their relationships, look through either an atlas or a neuroanatomy program and try to identify them without labels. Remember that the plane of section may vary slightly – for example, the optic chiasm may appear in the same section as the anterior commissure. You should still be able to identify structures based on their shape (such as the LGN), their appearance (the scrolled hippocampus), or their relationship to the ventricles (the caudate and thalamus).


Basic Visual Pathway

A. The Pathway

Vision is generated by photoreceptors in the retina, a layer of cells at the back of the eye. The information leaves the eye by way of the optic nerve, and there is a partial crossing of axons at the optic chiasm. After the chiasm, the axons are called the optic tract. The optic tract wraps around the midbrain to get to the lateral geniculate nucleus (LGN), where all the axons must synapse. From there, the LGN axons fan out through the deep white matter of the brain as the optic radiations, which will ultimately travel to primary visual cortex, at the back of the brain.

B. Visual Fields

Information about the world enters both eyes with a great deal of overlap. Try closing one eye, and you will find that your range of vision in the remaining eye is mainly limited by your nose. The image projected onto your retina can be cut down the middle, with the fovea defining the center. Now you have essentially two halves of the retina, a left half and a right half. Generally, the halves are referred to as a temporal half (next to your temple) and a nasal half (next to your nose). 

Visual images are inverted as they pass through the lens. Therefore, in your right eye, the nasal retina sees the right half of the world, while the temporal retina sees the left half of the world. Notice also that the right nasal retina and the left temporal retina see pretty much the same thing. If you drew a line through the world at your nose, they would see everything to the right of that line. That field of view is called the right hemifield.

So, what you see is divided into right and left hemifields. Each eye gets information from both hemifields. For every object that you can see, both eyes are actually seeing it – this is crucial for depth perception – but the image will be falling on one nasal retina and one temporal retina.

Why bother to divide the retinas at all? Recall that the brain works on a crossed wires system. The left half of the brain controls the right side of the body, and vice versa. Therefore the left half of the brain is only interested in visual input from the right side of the world. To insure that the brain doesn't get extraneous information, the fibers from the retina sort themselves out to separate right hemifield from left hemifield. Specifically, fibers from the nasal retinas cross over at the optic chiasm – whereas the temporal retinas, already positioned to see the opposite side of the world, do not cross. Here is what it looks like:

The practical consequences of this crossing are that damaging the visual system before the chiasm will affect one eye, both hemifields – analogous to closing one eye. Damaging the pathway after the chiasm, though, will damage parts of both eyes, and only one hemifield. There is no easy way to imagine what this would look like. Your field of view would be only 90°, from straight ahead to one side.

C. Lesions

The easiest way to demonstrate to yourself the consequences of lesions is to strike through a pathway, follow the fibers back to the retina, and see what was affected. Notice that there are lines and numbers drawn on the visual field diagram. For each "cut", determine what parts of the patient's visual field will be affected. The way to record a loss of visual field is with two circles, called "perimetry charts" as below. You can think of these circles as a pair of goggles that the patient is looking through, and you blacken those parts of the goggles where vision is lost. This is done separately for each eye, and drawn from the patient's perspective – the right circle represents the right eye. For example:


Lesion 1: This is analogous to losing an eye. One eye is completely blacked out.

Lesion 2: Here you have only cut inputs from the nasal retinas, so you would lose peripheral vision on both sides. This can be caused by a pituitary tumor (the pituitary lies just under the optic chiasm). 

Lesion 3: This lesion represents the loss of the left hemifield. Both eyes will be blind to anything on the left side of the world (assuming the eyes are pointed straight ahead). 

What about the last 3 lesions? To figure these out, you need to know about Meyer's loop and the optic radiations. The optic radiations follow a very wide three dimensional arc. Here is how the radiations are conventionally drawn, and how they look from the side:

You can see that the longer loop actually dives into the temporal lobe before it heads back to the occipital lobe. This group of fibers is called Meyer's loop. Recall that, since the lens inverts all images, the lower half of the retina sees the upper half of the world. This orientation is preserved through the pathway, so that the lower optic radiations, or Meyer's loop, are carrying information from the upper visual world.

Lesion 4: Meyer's loop has been cut, so vision will be lost in the upper visual world, but only in the left hemifield.

Lesion 5: Here the parietal portion of the optic radiations were cut, so you would affect the lower visual world on one side.

Lesion 6: At first this seems to be a straightforward loss of one hemifield. However, a curious phenomenon results when cortex itself is lesioned. 

Vision at the fovea is spared, perhaps because there is such a large representation of the fovea in the cortex, or perhaps due to overlapping blood supply. The loss of vision is not a complete hemifield, then, but a notched hemifield. This phenomenon is called macular sparing.


D. Anatomy

You should be able to follow the visual pathway through coronal or horizontal sections. In a coronal series, the most rostral thing you will see is the optic chiasm. The optic tracts will diverge and sneak up laterally around the cerebral peduncles before diving into the LGN. Don't confuse the optic chiasm with the anterior commissure; the chiasm will always hang down from the base of the brain, while the commissure will be embedded in tissue.

In horizontal sections you can see the optic radiations clearly, and you can identify the general vicinity of visual cortex. First find the calcarine sulcus on the medial surface of the occipital lobe. Primary visual cortex, or V1, is buried within this sulcus. In a fortuitous section, you may be able to see a fine white stripe running within the grey matter inside the sulcus. This stripe marks V1, and gives it a third name, striate cortex.

Basic somatosensory pathway

A. Overview

The somatosensory system includes multiple types of sensation from the body – light touch, pain, pressure, temperature, and joint and muscle position sense (also called proprioception). However, these modalities are lumped into three different pathways in the spinal cord and have different targets in the brain. The first modality is called discriminative touch, which includes touch, pressure, and vibration perception, and enables us to "read" raised letters with our fingertips, or describe the shape and texture of an object without seeing it. The second grouping is pain and temperature, which is just what it sounds like, and also includes the sensations of itch and tickle. The third modality is called proprioception, and includes receptors for what happens below the body surface: muscle stretch, joint position, tendon tension, etc. This modality primarily targets the cerebellum, which needs minute-by-minute feedback on what the muscles are doing.

These modalities differ in their receptors, pathways, and targets, and also in the level of crossing. Any sensory system going to the cerebral cortex will have to cross over at some point, because the cerebral cortex operates on a contralateral (opposite side) basis. The discriminative touch system crosses high – in the medulla. The pain system crosses low – in the spinal cord. The proprioceptive system is going to the cerebellum, which (surprise!) works ipsilaterally (same side). Therefore this system doesn't cross.

B. Discriminative Touch System

As an introduction to the somatosensory system, we will start by looking in some detail at the discriminative touch system. The system that is carried in the spinal cord includes the entire body from the neck down; face information is carried by cranial nerves, and we will come back to it later. Overall, the pathway looks like this:

Sensation enters the periphery via sensory axons. All sensory neurons have their cell bodies sitting outside the spinal cord in a clump called a dorsal root ganglion. There is one such ganglion for every spinal nerve. The sensory neurons are unique because unlike most neurons, the signal does not pass through the cell body. Instead the cell body sits off to one side, without dendrites, and the signal passes directly from the distal axon process to the proximal process.

The proximal end of the axon enters the dorsal half of the spinal cord, and immediately turns up the cord towards the brain. These axons are called the primary afferents (pink), because they are the same axons that brought the signal into the cord. (In general, afferent means towards the brain, and efferent means away from it.) The axons ascend in the dorsal white matter of the spinal cord.

At the medulla, the primary afferents finally synapse. The neurons receiving the synapse are now called the secondary afferents (purple). The secondary afferents cross immediately, and form a new tract on the other side of the brainstem.

This tract of secondary afferents will ascend all the way to the thalamus, which is the clearinghouse for eveything that wants to get into cortex. Once in thalamus, they will synapse, and a third and final neuron (lavender) will go to cerebral cortex, the final target.

C. Names and Faces

Now let's give names and images to the pathways and nuclei.

The location of the pathway in the spinal cord has several names. Since the tracts are on the dorsal side of the cord, they are sometimes called the dorsal columns. In upright humans, we call dorsal "posterior", so they are also called the posterior columns. Finally, they have Latin names. If we look at a cervical cord section (below) the posterior columns can actually be divided into two separate tracts. The midline tracts are tall and thin, and were given the name gracile fasciculus (gracile means slender, and fasciculus means a collection of axons). The outer tracts are more wedge shaped, and were given the name cuneate fasciculus (cuneate means wedge-shaped).

 The gracile fasciculus is carrying all of the information from the lower half of the body (legs and trunk), while the cuneate fasciculus is carrying information from the upper half (arms and trunk). This explains why you will only see the cuneate fasciculus in thoracic and cervical sections, even though the gracile fasciculus starts down in the sacral cord.

In the medulla, each tract synapses in a nucleus of the same name. The gracile fasciculus axons synapse in the gracile nucleus, and the cuneate axons synapse in the cuneate nucleus.

The secondary afferents leave these nuclei and immediately cross, lining up in the ventral medulla. The new tract that they form is called the medial lemniscus ("midline ribbon"), and it will ascend all the way through the brainstem. Here is how it looks in the upper medulla: 

In the pons, the medial lemniscus begins to flatten out as the pontine nuclei enlarge beneath it.

By the time we get to the midbrain, the medial lemniscus is getting pushed way up laterally and dorsally, which will position it to enter the thalamus.

 Once in the thalamus, the secondary afferents synapse in a thalamic nucleus called the ventrolateral posterior nucleus (VPL). The thalamocortical afferents (from thalamus to cortex) travel up through the internal capsule to get to primary somatosensory cortex, the end of the pathway.

Primary somatosensory cortex is located in the post-central gyrus, which is the fold of cortex just posterior to the central sulcus.


D. Diagrammatic Review

Here is the entire pathway in schematic form: 


Basic Motor Pathway

A. Overview

The motor pathways are pathways which originate in the brain or brainstem and descend down the spinal cord to control the a-motor neurons. These large neurons in the ventral horns of the spinal cord send their axons out via the spinal roots and directly control the muscles. The motor pathways can control posture, reflexes, and muscle tone, as well as the conscious voluntary movements that we think of when we hear "motor system". The most famous pathway is the so called "pyramidal system", which begins with the large pyramidal neurons of the motor cortex, travels through the pyramids of the brainstem, (somewhere in here there is a coincidence), and finally ends on or near the a-motor neurons. This system is extremely important clinically, as strokes often affect the motor system. Therefore it is crucial to understand the anatomy of the motor pathway.

B. Anatomy

The primary motor pathway is also called the corticospinal pathway. As all such pathways are named from beginning to end, this pathway starts in cortex and ends in the spine. Specifically, it starts in the precentral gyrus, the fold of cortex just anterior to the central sulcus.

The precentral gyrus has many names: primary motor cortex, Brodmann's area 4, M1, etc. It provides the bulk of the corticospinal tract, but other cortical areas contribute as well. One such area is area 3a, part of primary somatosensory cortex, which is hidden down inside the central sulcus.

If we take a section through the central sulcus, we can see subtle differences between the pre- and post-central gyri. All areas of cerebral cortex have six varying layers of cells, from the most superficial and cell-free layer I to the deep layer VI. Each layer has a slightly different cellular makeup, and the thicknesses of the layers vary with cortical area. The postcentral gyrus, also known as primary somatosensory cortex, has a distinct layer IV – across cortical areas, layer IV generally receives sensory information. In the precentral gyrus, the motor cortex doesn't receive much in the way of sensory input, so layer IV is indistinct. However, layer V, which is generally responsible for sending information down to the brainstem and beyond, is very prominent in motor cortex. 

 The corticospinal tract originates as the axons of pyramidal neurons in layer V of (mainly) primary motor cortex. In general, the farther the axon has to go, the larger the neuron. In the precentral gyrus you can see some especially large neurons, visible even at low magnification. These neurons are called Betz cells, and were once thought to be the sole source of the corticospinal tract. We now know that they are only a subset of the pyramidal neurons which make up the tract. Pyramidal neurons, incidentally, occur in all types of cortex – it is just a morphological name for large neurons that are triangular in shape, pointing a long apical dendrite toward the surface of the brain.

Once the axons leave the pyramidal cells, they enter the white matter just below layer VI. Every gyrus in the brain has this core of white matter, which contains all of the axons entering or exiting the gyrus. As you get deeper into the brain, all of these slips of white matter coalesce to form one large body of axons, the corona radiata, "radiating crown". As you get still deeper into the hemispheres, the corona radiata dives into the deep nuclei of the brain, the caudate and putamen, splitting them in two. At this point, all of these axons are called the internal capsule.

The internal capsule is a major two-way highway, and very vulnerable to strokes. Sensory information travels up it on the way from the thalamus to the cortex, and motor information travels through on the way down to the spine. As you saw in the horizontal sections at the beginning of the course, the internal capsule has an anterior and posterior limb. The motor and somatosensory information travels through the posterior limb

If you were to follow horizontal sections down through the brain, at around the level where the midbrain begins, you would see the internal capsule coalesce into a tight bundle to exit the cerebral hemispheres. At this point the axons are called the cerebral peduncles, or the "stalks" of the cerebrum. The peduncles make up the floor of the midbrain, and contain all of the descending axons going to the brainstem or spine. The peduncles, unlike the internal capsule, are largely one-way; most of the axons in them are heading south. The ascending, sensory axons take other routes to get to the thalamus.

Once midbrain gives way to pons, two things happen to the peduncles. One, many of the axons from cortex were actually headed for the pons (the "corticopontine" fibers, of course), so they get off and synapse. Two, the remaining corticospinal axons get a little fragmented in the pons, so they are no longer visible as a nice tight bundle. They can be seen as several smaller bundles, though. 

 In the medulla, the fibers come together again as the pyramids. The pyramids were actually named as landmarks on the surface of the brainstem – on a human brainstem you can clearly see them as two ridges running down the ventral midline. The pyramids run the entire length of the medulla, large uninterrupted axon tracts on the ventral surface.

 At the very caudal-most end of the medulla, right about at the point where you have to start calling it cervical spinal cord, the fibers in the pyramids cross. The cerebrum controls the opposite side of the body, so it had to happen sometime, didn't it? The crossing event is called the decussation of the pyramids, and you can identify it by the way the midline groove is suddenly way off the midline. In any single section, it looks like only one side is crossing, but this is a sectioning artifact. Large bundles of axons take turns crossing, much like your fingers interlace when you clasp your hands. As you section down through the decussation, the midline fissure will bend first to one side, then the other. 

As each individual fiber crosses (remember, these are still the same axons we started with, from the pyramidal neurons of area 4!), where does it go? The pyramids do not merely exchange places. Instead each crossing axon takes up residence in the lateral white matter of the spinal cord. By the time the decussation is completed, the corticospinal fibers reside in this new location, now called the lateral corticospinal tract.

From this position they dive into the grey matter of the spinal cord at their target levels. Those fibers controlling the arms, for example, get off in the cervical levels of the cord. Once in the ventral horn they synapse either on interneurons (most common) or directly on the a-motor neurons. They preferentially innervate the limbs and distal muscles.

C. Nomenclature

As you may have learned in anatomy, if there is a greater horn of Ubu, there is probably also a lesser horn of Ubu. (Fictional, don't look it up.) Likewise, if there is a lateral corticospinal tract, there must also be a medial one. Indeed there is, only it is called the anterior corticospinal tract. Take comfort in the fact that it does actually lie medially. These fibers were part of the original corticospinal tract, and made up 15-20% of the pyramids, but at the decussation, they did not cross. As a result, in the spinal cord they are still sitting right where the pyramids were – ventrally, on either side of the midline. 

These fibers also dive into the ventral horns at appropriate levels, and they tend to innervate the muscles of the trunk. Fine finger movements and tap dancing are the exclusive domain of the lateral corticospinal tract, but push-ups and hula-hooping rely more on the anterior corticospinal tracts.

D. Summary

Here is a diagram summarizing the two main pathways of the voluntary motor system:


E. Clinical Notes

In motor cortex, the body is mapped out across the extent of the gyrus. Control of the feet lies near the midline at the top of the gyrus, whereas the lateral side of the gyrus controls the hands and face. Because the body parts are spread so widely in cortex, cortical strokes are rarely big enough to affect an entire half of the body. Instead, the hands or face, which take up the most cortical area, are preferentially affected. Strokes in the internal capsule are a different story. Fibers are bundled together so closely that a small stroke can in fact paralyze an entire side of the body – this is called hemiplegia (half-paralysis) or hemiparesis (half-weakness). If a stroke occurs in the brainstem, affecting the pyramids, the hemiparesis will often be accompanied by other symptoms or "neighborhood signs"; the brainstem is a very crowded place.

Although the cortex is primarily concerned with the contralateral (opposite) side of the body, some muscle groups get innervation from both hemispheres. This bilateral innervation protects the muscle groups in case of stroke. Most of the muscles in the trunk are bilaterally innervated, so that even hemiplegic patients can hold their torsos upright. For some reason, the forehead also receives bilateral innervation, which can be a key clue in determining if a patient's facial paralysis is due to a cerebral stroke or a peripheral nerve injury. In a cerebral stroke patient, only the lower half of the face (on one side) will be affected. In a patient with Bell's palsy (a temporary inflammation of the facial nerve), the entire side of the face will be affected.


Eye and retina

A. Overview

Light enters the pupil, is focused and inverted by the cornea and lens, and is projected onto the back of the eye. At the back of the eye lies the retina, seven layers of alternating cells and processes which convert a light signal into a neural signal ("signal transduction"). The actual photoreceptors are the rods and cones, but the cells that transmit to the brain are the ganglion cells. The axons of these ganglion cells make up the optic nerve, the single route by which information leaves the eye.


B. Structures at the Anterior Pole of the Eye

 Moving parts of the eye:

  • The iris is really a shutter that can be closed down to regulate the amount of light entering the eye. This process is controlled by two muscles with distinct innervation:
    • the pupillary sphincter muscle constricts the pupil like a purse-string, and is under the control of the parasympathetic system. Therefore it is innervated by fibers from the oculomotor nerve which originate in the Edinger-Westphal nucleus of the midbrain.
    • the pupillary dilator muscle is composed of radial fibers which pull the pupil open, and is controlled by the sympathetic system. Therefore it is innervated by post-ganglionic sympathetics from the superior cervical ganglion. Remember that the pre-ganglionics come from T1.
  • The lens is a naturally elastic structure. If it had its way, it would round up into a more spherical shape. Under normal conditions, however, an array of radial fibers – the zonule fibers – hold the lens stretched out into a more disc-like shape. This shape allows for far-focusing. What happens when you need to near-focus? At this point the ciliary body, a hoop-like structure that supports the zonule fibers, comes into play. Imagine a spiderweb built into the opening of a drawstring purse, suspending a disk in the opening. When the purse is open, the spiderweb is taut. If you pull the drawstring, however, the web will go slack and collapse on itself. The ciliary body is the drawstring purse, in this analogy. The ciliary muscle within it is the drawstring. When the ciliary muscle contracts (this is also under parasympathetic control), the zonule fibers go slack, the suspended lens is released from their tension, and it is free to round up. This change is necessary for near-focusing. The entire process of adjusting the focus to different distances is called accommodation.


C. The Retina

The retina is a seven-layered structure involved in signal transduction. In general, dark "nuclear" or "cell" layers contain cell bodies, while pale "plexiform" layers contain axons and dendrites.

Trace the signal through the retina: – Light enters from the GCL side first, and must penetrate all cell types before reaching the rods and cones. – The outer segments of the rods and cones transduce the light and send the signal through the cell bodies of the ONL and out to their axons. – In the OPL photoreceptor axons contact the dendrites of bipolar cells and horizontal cells. Horizontal cells are interneurons which aid in signal processing. – The bipolar cells in the INL process input from photoreceptors and horizontal cells, and transmit the signal to their axons. – In the IPL, bipolar axons contact ganglion cell dendrites and amacrine cells, another class of interneurons.
- The ganglion cells of the GCL send their axons through the OFL to the optic disk to make up the optic nerve. They travel all the way to the lateral geniculate nucleus.

D. Specializations of the Retina

The fovea defines the center of the retina, and is the region of highest visual acuity. The fovea is directed towards whatever object you wish to study most closely – this sentence, at the moment. In the fovea there are almost exclusively cones, and they are at their highest density.

The ratio of ganglion cells : photoreceptors is about 2 :1 here, the highest in the eye. In addition, at the fovea all of the other cell types squeeze out of the way to allow the most light to hit the cones. This makes the fovea visible microscopically. The blood vessels also skirt a wide margin around the fovea. The area in and around the fovea has a pale yellow pigmentation that is visible through an ophthalmoscope, and is called the macula.

 The ganglion cell axons all leave the eyeball at one location, the optic disk. At the optic disk all photoreceptors and accessory cells are pushed aside so the axons can penetrate the choroid and the sclera. This creates a hole in our vision, the blind spot. Normally each eye covers for the blind spot of the other, and the brain fills in missing information with whatever pattern surrounds the hole. Therefore we are not conscious of the blind spot.

Photoreceptors are not distributed evenly throughout the retina. Most cones lie in the fovea, whereas peripheral vision is dominated by rods. Overall, rods greatly outnumber cones. Review the characteristics of rods (black and white vision, very sensitive to low light) and cones (color vision, not so sensitive) and explain these phenomena: 1. To see a faint star, you cannot look directly at it, but must look slightly to the side.
2. A person with macular degeneration can become functionally blind, yet their night vision is not really affected. How would their color perception be?

E. Interesting Anatomical Facts

The cornea is continuous with the sclera, which in turn is continuous with the dura.
- The choroid, a highly vascular, highly pigmented layer between the sclera and the retina, is continuous with the ciliary body and the iris. Do not confuse it with the pigment epithelium.
- The pigment epithelium is a single cell layer thick, and comes from the outer layer of the original optic cup (a classic embryological "pushed-in ball"). In the mature retina it is pushed directly up next to the neural retina, which came from the inner layer of the optic cup. They are not fused together, however, and can separate along the old plane – a "separated" or "detached" retina.

F. Signal Processing in the Retina

If you were to record from a photoreceptor, you would find that it was "ON" (hyperpolarized, paradoxically) whenever light shone on it. If you recorded from a ganglion cell instead, you would find that diffuse light did little to the cell. However, the cell would respond well to a small spot of light, a small ring of light, or a light-dark edge. We say that this cell has a center-surround receptive field – the center must be mainly light and the surround mainly dark, or vice versa. What happens between the outer segment and the ganglion cell? This complex receptive field is created by the interneurons of the retina: the bipolar cells and the horizontal cells, primarily.

Let's trace a signal through:

1. Light hyperpolarizes the cone (or rod). For simplicity's sake, we will just say that turns ON the cone, and thereby excites the bipolar cell directly underneath. That bipolar cell then excites its ganglion cell. The same thing is happening to neighbor cells.

2. However, here's the trick. The neighbor cones also excite horizontal cells. The horizontal cells send processes laterally and inhibit the center bipolar cell.

So, what does diffuse light do? It excites the central bipolar cell, but also inhibits it via the neighbors. Result – the ganglion cell does not get excited. It continues to tick along at its normal, tonic rate.

3. A small spot of light, however, excites the bipolar cell but not its neighbors. There is no inhibition, so it is free to get really excited and excite the ganglion cell, which fires like crazy.

4. A ring of light excites only the neighbors. Now, the bipolar cell is strongly inhibited, with no excitation. In response to this strong silencing of the bipolar cell, the ganglion cell shuts down as well. It will not turn on again until the light is turned off, at which time you will see a rebound "off-response".

This is an ON-center cell.

The reverse of this entire scenario can be created by reversing all the signals (which we can do with different receptors to the same neurotransmitter).


This unique center-surround receptive field is also a property of lateral geniculate neurons. Things get even more complicated up in the cortex.

What is the point? Well, our entire visual system exists to see borders and contours. We see the world as a pattern of lines, even things as complex as a face. We judge colors and brightness by comparison, not by any absolute scale. (Don't believe it? Put that teal scarf next to a blue shirt, you'll call it green. On a green coat, you'll call it blue.) This system of lateral inhibition in the retina is the first step towards sharpening contours and picking up on borders between light and dark. Diffuse light is ignored by the ganglion cell, but a sharp dot will really turn it on. Higher up in the cortex, all these dots will be combined into lines, which will be combined into curves, etc, etc.

Central visual pathways

A. After the Retina

Once the ganglion cell axons leave the retina, they travel through the optic nerve to the optic chiasm, a partial crossing of the axons. At the optic chiasm the left and right visual worlds are separated. After the chiasm, the fibers are called the optic tract. The optic tract wraps around the cerebral peduncles of the midbrain to get to the lateral geniculate nucleus (LGN). The LGN is really a part of the thalamus, and remember that nothing gets up to cortex without synapsing in thalamus first (if the cortex is the boss, the thalamus is an excellent secretary). Almost all of the optic tract axons, therefore, synapse in the LGN. The remaining few branch off to synapse in nuclei of the midbrain: the superior colliculi and the pretectal area. We will come back to these.

B. The lateral geniculate nucleus:

"Geniculate" means knee-shaped, and it is a pretty accurate description of the LGN. No matter how you slice it, the LGN looks like a striped Andy-Capp-hat. The stripes are actually layers, and there should be six of them in most parts of the LGN. Each layer receives inputs from a different eye: 3 layers for the left eye and 3 layers for the right. (Keep in mind, each LGN gets information from 1 hemifield, but 2 eyes.) These layers alternate, so if you were to label the axons from just one eye, you would see alternate stripes labeled, as below. 

There is a second aspect of organization in the LGN. The outer 4 layers are composed of small cells, and correspondingly, receive inputs from the small ganglion cells of the retina. These layers are called the parvocellular layers. The magnocellular layers, on the other hand, are composed of large cells and receive their input from large ganglion cells. We will return to the reason for this segregation at the end of the section.

C. To the Cortex

The neurons in the LGN send their axons directly to V1 (primary visual cortex, striate cortex, area 17) via the optic radiations. This highway of visual information courses through the white matter of the temporal and parietal lobes, and can be very vulnerable to strokes. Once the axons reach V1, they terminate primarily in a single sub-layer of cortex.

Remember that all cortical areas in the cerebrum are composed of six basic layers, but that each specific area of cortex may have modifications of layers to best serve its function. It was on the basis of layer appearance and cell types alone that Brodmann first subdivided the cortex into over 50 areas. These areas are known today to correspond to functionally distinct areas – area 17 is primary visual cortex, for example. As you struggle to identify layers 1-6 in any piece of cortex, ponder the fact that this man identified 50 different subtleties of those layers. It's awe inspiring.

The layers of V1 are specialized in one primary way – layer 4 has been expanded into 4 sublayers: 4A, 4B, 4Ca, and 4Cb. Layer 4A is a dark layer, while the deeper 4B is a very pale layer full of myelin. 4B is actually visible without a microscope – it is the line of Gennari, the white stripe that gives V1 its other name, striate cortex. Layer 4C is important because it receives most of the input from the LGN. Due to these specializations, you too can see a transition between Brodmann areas. Follow along the 4B stripe, and you will see it suddenly disappear into a more compact layer 4. This is the transition between areas V1 and V2 (secondary visual cortex, area 18).


D. Ocular Dominance Stripes

We have mentioned that the LGN axons enter into layer 4C. However, recall that the LGN is segregated by eye. This separation is maintained as the axons enter the cortex. Each cluster of axons from each LGN layer spreads out in a little column within 4C.

  As the signal is transmitted to upper layers of cortex, the information from the two eyes is mixed and binocular vision is created, but here in 4C the two eyes are still entirely separate. Therefore, if you could label the inputs from a single eye, in 4C you would see little pillars of label. If you were to cut tangentially (parallel to the surface) through layer 4C, you would see that all those pillars line up next to each other and form tiger stripes. These are the ocular dominance stripes.

E. What Exactly is Cytochrome Oxidase?

Cytochrome oxidase is a staining technique which preferentially stains metabolically active neurons. This is a useful tool in looking at ocular dominance columns: if an eye is surgically closed in an experimental animal, a cytochrome oxidase stain will reveal the LGN axons carrying signals from the remaining, active eye. This is how one eye can be selectively stained, as in the picture to the right. However, researchers staining with cytochrome oxidase happened upon another property of V1. In layer 3, certain areas always seemed to stain darkly, regardless of the status of the eyes. Tangential sections through layer 3 showed a pattern similar to leopard spots. These areas of stain were named blobs, and the pale areas around them, interblobs. It has since been shown that they represent a division of labor within the cortex: specifically, the blobs are more involved in color processing than the interblobs.


F. Receptive Fields in V1

Recall that the receptive fields of both ganglion cells and LGN neurons were center-surround, and that they responded optimally to points of light. Neurons in the cortex, however, respond very poorly to points of light. The optimal stimulus for most cortical neurons turns out to be a bar of light, in a very specific orientation. How did this come about? One hypothesis is that the key is in how the LGN axons converge on the cortical neurons.

Take three LGN neurons responding to adjacent ganglion cells. Their ON-center receptive fields are represented by this array of donuts.

Now hook all three of these LGN neurons up to one cortical neuron, and dictate that all 3 must be excited at once to evoke a response in cortex.

What would be the absolute optimal stimulus to drive the cortical neuron nuts? Three points of light, right?

Three precisely spaced points of light are actually not so likely in nature, but how about a line?

Sure enough, a bar of light will turn on this cortical neuron.

How about a bar oriented 90° to the right? You can see that this stimulus would be too weak for the cortical neuron.

 The simplest type of receptive field in the cortex follows this arrangement closely. An optimal stimulus is a bar of light in the center of the receptive field, at some precise orientation. Other connections and convergences in other areas of cortex set up more and more complicated receptive fields, until single cells can be responsive only to the shape of a face. But really all of the information for that face entered your retina as nothing more than... ...a thousand points of light.

G. Division of Labor in the Visual System

What we see can be divided into several categories of vision: color, linear pattern, motion, etc. The perception of these different categories requires a wide variety of equipment, and some of the divisions are made as early as the retina. For example, rods see only black and white, and can function in dim light, whereas cones can see all colors but require full light. There are at least two types of ganglion cells as well. There are small ganglion cells that dominate in the fovea: they are color sensitive and are "fine-grained", meaning their receptive fields are small enough that they can pick up a high level of detail. These small cells are called P cells (P for parvo for small). The second type of ganglion cells have large dendritic arrays, and receive information from a wide radius of bipolar cells. They are mostly found in the peripheral retina, are not color-sensitive, and are "coarse-grained" and relatively insensitive to detail. Their main asset is that they are sensitive to motion – you can imagine that due to their width they can track a signal flashing across several bipolar cells. These are the M cells (M for magno ).

These two types of information, motion vs. color and form, are maintained in separate compartments all the way up the visual pathway. They are kept in separate layers in the LGN, enter V1 via separate sublayers (4Ca vs. 4Cb), and after passing through V2, go on to separate areas of associative cortex. In the end, the parietal visual cortical areas (such as MT and PP) end up dealing with motion of objects, navigation through the world, and spatial reasoning (which is essentially moving things around in your head). Temporal visual areas (such as V4 and IT) are involved with the complex perception of patterns and forms as recognizable objects.

In summary, when your Aunt Edna goes streaking by you after unwisely taking a dip in the snake-infested pond out back, your color/form pathway will identify her as Aunt Edna; your motion pathway will tell you which way she went. Any emotional response you attach to this event will be mediated by the amygdala, incidentally.

H. The Pupillary Light Reflex

Way back at the beginning of this section, there was mention of a few optic tract fibers which bypassed the LGN entirely, traveling instead to the less glamorous but equally essential midbrain. One of their targets in the midbrain is the pretectal area, which mediates the pupillary light reflex. This reflex can be demonstrated by shining a light in one eye; if all is working correctly, both pupils will constrict.

 Light enters the retina and from there travels directly to the pretectal area. After synapsing, the information is sent to the Edinger-Westphal nuclei on both sides of the midbrain – this is the crucial step in ensuring that both eyes react to light. The Edinger-Westphal nuclei, via the IIIrd nerve, control the pupillary constrictors that narrow the pupils. Knowledge of all this enables you to test the status of your patient's visual system by shining a light into each eye.

For example, if you test each eye, and no matter where you shine the light, the left pupil constricts and the right one remains dilated, what is your conclusion? There must be a problem with constriction on the right, such as IIIrd nerve damage. BUT, what if shining light into the left eye produces bilateral constriction, and shining light into the right eye produces no constriction? Here the problem must be with the right optic nerve itself, or possibly the right pretectal area. What would happen if you made a cut down the midline of the midbrain, severing right from left?


Auditory and vestibular systems

A. The Inner Ear

The auditory and vestibular systems are intimately connected. The receptors for both are located in the temporal bone, in a convoluted chamber called the bony labyrinth. A delicate continuous membrane is suspended within the bony labyrinth, creating a second chamber within the first. This chamber is called the membranous labyrinth. The entire fluid-filled structure is called the inner ear.

The inner ear has two membrane-covered outlets into the air-filled middle ear – the oval window and the round window. The oval window is filled by the plate of the stapes, the third middle ear bone. The stapes vibrates in response to vibrations of the eardrum, setting the fluid of the inner ear sloshing back and forth. The round window serves as a pressure valve, bulging outward as pressure rises in the inner ear.


The oval window opens into a large central area within the inner ear called the vestibule. All of the inner ear organs branch off from this central chamber. On one side is the cochlea, on the other the semicircular canals. The utricle and saccule, additional vestibular organs, are adjacent to the vestibule.

The membranous labyrinth is filled with a special fluid called endolymph. Endolymph is very similar to intracellular fluid: it is high in potassium and low in sodium. The ionic composition is necessary for vestibular and auditory hair cells to function optimally. The space between the membranous and bony labyrinths is filled with perilymph, which is very much like normal cerebral spinal fluid.

B. Auditory Transduction

The transduction of sound into a neural signal occurs in the cochlea. If we were to unroll the snail-shaped cochlea, it would look like this: 

As the stapes vibrates the oval window, the perilymph sloshes back and forth, vibrating the round window in a complementary rhythm. The membranous labyrinth is caught between the two, and bounces up and down with all this sloshing. Now let's take a closer look at the membranous labyrinth. If we cut the cochlea in cross section, it looks like this:

The membranous labyrinth of the cochlea encloses the endolymph-filled scala media. The two compartments of the bony labyrinth, which house the perilymph, are called the scalae vestibuli and tympani. Within the scala media is the receptor organ, the organ of Corti. It rests on part of the membranous labyrinth, the basilar membrane.

A single turn of the cochlea has been outlined in blue.

You can see the auditory nerve exiting at the base of the cochlea; it will travel through the temporal bone to the brainstem.

The auditory hair cells sit within the organ of Corti. There are inner hair cells, which are the auditory receptors, and outer hair cells, which help to "tune" the cochlea, as well as supporting cells. The sensitive stereocilia of the inner hair cells are embedded in a membrane called the tectorial membrane. As the basilar membrane bounces up and down, the fine stereocilia are sheared back and forth under the tectorial membrane. When the stereocilia are pulled in the right direction, the hair cell depolarizes. This signal is transmitted to a nerve process lying under the organ of Corti. This neuron transmits the signal back along the auditory nerve to the brainstem. As with almost all sensory neurons (the exception is in the retina), its cell body lies outside the CNS in a ganglion. In this case, the ganglion is stretched out along the spiralling center axis of the cochlea, and is named the spiral ganglion.

You can see most of the structures in this higher magnification of the organ of Corti; unfortunately, the inner hair cells have been artifactually pulled away from the tectorial membrane.

The basilar membrane is actually thinner and narrower at the base of the cochlea than at the tip (apex), which seems backwards given that the cochlea is widest at the base. The properties of the basilar membrane change as its shape changes; just as with guitar strings, thin things vibrate to high pitches, and thick things vibrate to low pitches. This means that the basilar membrane vibrates to high frequencies at the base of the cochlea and to low frequencies at the apex. A hair cell at the base of the cochlea will respond best to high frequencies, since at those frequencies the basilar membrane underneath it will vibrate the most. The key idea is that although the hair cells are arranged in order along the basilar membrane, from high-frequency to low-frequency, it is the properties of the basilar membrane that set up this gradient, not the properties of the hair cells.

Our ability to discriminate two close frequencies is actually much better than one would predict just from the mechanics of the basilar membrane. One theory to explain the mystery is that the outer hair cells help to "sharpen the tuning". Outer hair cells can actually move (change length) in response to nerve stimulation. If they could push the basilar membrane up and down, they could amplify or damp vibrations at will, making the inner hair cells more or less responsive. (Just like you can push a child higher and higher on a swing or bring her to a halt – it's all in when you push.) An interesting philosophical question here is, if the outer hair cells can move the basilar membrane, can that in turn move the oval window? And the stapes? And the eardrum? Can the ear, in fact, work in reverse and become a speaker? You may laugh, but there has been at least one case in the history of medicine of a patient complaining of persistent whispering in her ear. She was dismissed as crazy, until one obliging doctor finally put his stethoscope to her ear and listened. He could hear the whispering too. You can draw your own moral from this story.

However, most cases of tinnitus (a persistent ringing, whistling, or roaring in the ears) are not audible to the examiner. Little is known about the phenomenon, which is unfortunate because it can be very distressing to the sufferer.

C. Central Auditory Pathways

The auditory nerve carries the signal into the brainstem and synapses in the cochlear nucleus. From the cochlear nucleus, auditory information is split into at least two streams, much like the visual pathways are split into motion and form processing. Auditory nerve fibers going to the ventral cochlear nucleus synapse on their target cells with giant, hand-like terminals. Something about this tight connection allows the timing of the signal to be preserved to the microsecond (action potentials are on the order of milliseconds, so it is no mean feat). The ventral cochlear nucleus cells then project to a collection of nuclei in the medulla called the superior olive. In the superior olive, the minute differences in the timing and loudness of the sound in each ear are compared, and from this you can determine the direction the sound came from. The superior olive then projects up to the inferior colliculus via a fiber tract called the lateral lemniscus.

The second stream of information starts in the dorsal cochlear nucleus. Unlike the exquisitely time-sensitive localization pathway, this stream analyzes the quality of sound. The dorsal cochlear nucleus, with fairly complex circuitry, picks apart the tiny frequency differences which make "bet" sound different from "bat" and "debt". This pathway projects directly to the inferior colliculus, also via the lateral lemniscus.

Notice that both pathways are bilateral. The consequence of this is that lesions anywhere along the pathway usually have no obvious effect on hearing. Deafness is essentially only caused by damage to the middle ear, cochlea, or auditory nerve.

From the inferior colliculus, both streams of information proceed to sensory thalamus. The auditory nucleus of thalamus is the medial geniculate nucleus. The medial geniculate projects to primary auditory cortex, located on the banks of the temporal lobes.

Keep in mind, as you try to remember this pathway, that the auditory nuclei all seem to have counterparts in other systems, making life confusing. Fibers from the cochlear nuclei and the superior olive (not the inferior) travel up the lateral lemniscus (not the medial) to the inferior colliculus (not the superior), and then to the medial geniculate (not the lateral). Try remembering the mnemonic, "S-L-I-M" .

D. The Vestibular System

The purpose of the vestibular system is to keep tabs on the position and motion of your head in space. There are really two components to monitoring motion, however. You must be able to detect rotation, such as what happens when you shake or nod your head. In physics, this is called angular acceleration. You must also be able to detect motion along a line – such as what happens when the elevator drops beneath you, or on a more subtle note, what happens when your body begins to lean to one side. This is called linear acceleration. The vestibular system is divided into two receptor organs to accomplish these tasks.

E. The Semicircular Canals

The semicircular canals detect angular acceleration. There are 3 canals, corresponding to the three dimensions in which you move, so that each canal detects motion in a single plane. Each canal is set up as shown below, as a continuous endolymph-filled hoop. The actual hair cells sit in a small swelling at the base called the ampula.

The hair cells are arranged as a single tuft that projects up into a gelatinous mass, the cupula. When you turn your head in the plane of the canal, the inertia of the endolymph causes it to slosh against the cupula, deflecting the hair cells. Now, if you were to keep turning in circles, eventually the fluid would catch up with the canal, and there would be no more pressure on the cupula. If you stopped spinning, the moving fluid would slosh up against a suddenly still cupula, and you would feel as though you were turning in the other direction. This is the explanation for the phenomenon you discovered when you were 5.

Naturally, you have the same arrangement (mirrored) on both sides of the head. Each tuft of hair cells is polarized – if you push it one way, it will be excited, but if you push it the other way, it will be inhibited. This means that the canals on either side of the head will generally be operating in a push-pull rhythm; when one is excited, the other is inhibited (see below). It is important that both sides agree as to what the head is doing. If there is disagreement, if both sides push at once, then you will feel debilitating vertigo and nausea. This is the reason that infections of the endolymph or damage to the inner ear can cause vertigo. However, if one vestibular nerve is cut, the brain will gradually get used to only listening to one side – this can actually be a treatment for intractable vertigo. 

A large role of the semicircular canal system is to keep your eyes still in space while your head moves around them. If you nod and shake and swivel your head, you will find that you have no trouble staying focused on this page. But hold a piece of paper in front of you and shake it around, and your eyes will not be able to keep up with the quick movements. The reason is that the semicircular canals exert direct control over the eyes, so they can directly compensate for head movements. Recall that the eye is controlled by three pairs of muscles; the medial and lateral rectus, the superior and inferior rectus, and the inferior and superior oblique. You may also remember that their directions of motion seemed to be at crazy diagonals. Those same crazy diagonals are matched closely by the three planes of the semicircular canals, so that a single canal (in general) interacts with a single muscle pair. The entire compensatory reflex is called the vestibulo-ocular reflex (VOR).

F. The VOR

Although the VOR works on all three muscle pairs, the medial-lateral rectus pair, coupled to the horizontal canal, is geometrically the easiest to draw. Here is the setup, looking down at a person's head:

The lateral rectus muscle will pull the eye laterally, and the medial rectus will pull the eye medially, both in the horizontal plane. The horizontal canal detects rotation in the horizontal plane.

If you move your head to the left, you will excite the left horizontal canal, inhibiting the right. To keep your eyes fixed on a stationary point, you need to fire the right lateral rectus and the left medial rectus, to move the eyes to the right.

The pathway is as follows: the vestibular nerve enters the brainstem and synapses in the vestibular nucleus. Cells that received information from the left horizontal canal project to the abducens nucleus on the right side, to stimulate the lateral rectus. They also project to the oculomotor nucleus on the left side, to stimulate the medial rectus. Although not shown on the diagram, the same vestibular cells also inhibit the opposing muscles (in this case, the right medial rectus, and the left lateral rectus).

What about the other side? The right horizontal canal is wired to the complementary set of muscles. Since it is inhibited, it will not excite its target muscles (the right medial rectus and the left lateral rectus), nor will it inhibit the muscles you want to use (the right lateral rectus and the left medial rectus). Got it? OK, then draw out what would happen if you turned your head to the right.

A great deal of the VOR axon traffic travels via a fiber highway called the MLF (medial longitudinal fasciculus). The integrity of this tract is crucial for the VOR to work properly. It is occasionally damaged by medial brainstem strokes.

G. The Utricle and Saccule

The utricle and saccule detect linear acceleration. Each organ has a sheet of hair cells (the macula) whose cilia are embedded in a gelatinous mass, just like the semicircular canals. Unlike the canals, however, this gel has a clump of small crystals embedded in it, called an otolith (yes, all along you've had rocks in your head). The otoliths provide the inertia, so that when you move to one side, the otolith-gel mass drags on the hair cells. Once you are moving at a constant speed, such as in a car, the otoliths come to equilibrium and you no longer perceive the motion.

The hair cells in the utricle and saccule are polarized, but they are arrayed in different directions so that a single sheet of hair cells can detect motion forward and back, side to side. Each macula can therefore cover two dimensions of movement. The utricle lays horizontally in the ear, and can detect any motion in the horizontal plane. The saccule is oriented vertically, so it can detect motion in the sagittal plane (up and down, forward and back).

A major role of the saccule and utricle is to keep you vertically oriented with respect to gravity. If your head and body start to tilt, the vestibular nuclei will automatically compensate with the correct postural adjustments. This is not just something that happens if the floor tilts – if you watch someone trying to stand still, you will notice constant small wavers and rocking back and forth. 


Somatosensory Pathways From the Body

A. Peripheral Receptors

There are three different categories (modalities) of the somatosensory system. The first, discriminative touch, is the perception of pressure, vibration, and texture. This system relies on four different receptors in the skin. They are:

1) Meissner's corpuscles 2) Pacinian corpuscles 3) Merkel's disks
4) Ruffini endings

The first two are considered rapidly adapting (they quickly stop firing in response to a constant stimulus) and the second two are considered slowly adapting (they do not stop firing). To put this into an example, if you lay your pen down in your palm, the Meissner's and Pacinian corpuscles will fire rapidly as it first touches down, to let you know something has landed. If the pen lays still, they will stop firing almost right away. The Merkel's and Ruffini endings, however, will continue to fire to let you know that something is still there.

The pain and temperature system does not have specialized receptor organs. Instead, it uses free nerve endings throughout skin, muscle, bone, and connective tissue to perceive changes in temperature and pain peptides. Although pain will result from damage to a free nerve ending, in reality most pain is a result of substances released by damaged tissues: prostaglandins, histamine, and substance P. The free nerve ending has receptors for these substances and lets you know (stridently) when tissue has been damaged.

The third modality, proprioceptive sensation, relies on receptors in muscles and joints. The muscle spindle is the major stretch receptor within muscles, and just like the cutaneous receptors, it has a rapidly-adapting and slowly-adapting component. (For more on the muscle spindle see "Spinal motor structures".) There are also Golgi tendon organs and joint afferents to monitor stresses and forces at the tendons and joints.

B. Axon Diameters

Sensory axons can be classified according to diameter and therefore conduction velocity. The largest and fastest axons are called Aa, and include some of the proprioceptive neurons, such as the stretch receptor. (Note: there is a separate, Roman numeral classification used for the proprioceptive axons, which will be covered in the section on muscle spindles.) The second largest group is called Ab, which includes all of the discriminative touch receptors. Pain and temperature include the third and fourth groups, Ad and C fibers. There are two subtypes of pain. "Fast pain", carried by the Ad fibers, is the instantaneous pain that makes your arm jerk back before you even realized you were burned. It is sharp and piercing and over quickly. "Slow pain" is carried by C fibers. C fibers are not only small, they are unmyelinated (the only sensory axons without myelin), so their conduction velocity is quite slow. Slow pain is primarily mediated by those tissue-damage peptides listed above, and can go on indefinitely. It is distressing, it can be dull and aching, and it does not trigger withdrawal reflexes like the fast pain. A perfect example of slow pain is when you stub your toe on the coffee table. You feel the jolt of impact (proprioception and Pacinian corpuscles), and you have approximately a heartbeat to think, "This is really going to hurt." That heartbeat is the C-fiber travel time from your toe to your brain. When the signal hits, the pain is severe and lasts for quite a while. It is, however, a nice demonstration of the relative conduction velocities of Aa and C fibers.

As the dorsal root enters the cord (all sensory information comes in via the dorsal root, and all sensory cell bodies are in the dorsal root ganglion), the fibers sort themselves out by diameter. The largest fibers enter the cord most medially, and the smallest fibers enter most laterally. From there, the three modalities take very different paths, so we must look at each one separately.

C. The Discriminative Touch System

The posterior columns should be a review from the "Basic somatosensory" section. Here is a schematic of the pathway, to remind you:

The key points are that the primary afferents ascend all the way to the medulla, on the ispilateral side of the cord, in the posterior columns. The secondary afferents cross in the medulla and ascend as the medial lemniscus. In the thalamus they synapse in the VPL (the ventroposterior lateral nucleus) and finally ascend to cortex.

D. The Pain and Temperature System

This system shares one major rule with the discriminative touch system: primary afferents synapse ipsilaterally, then secondary afferents cross. SYNAPSE, then CROSS. The crossings just occur at different levels.

Pain afferents (all of the following applies to temperature as well) enter the cord laterally, due to their small size, and synapse more or less immediately. "More or less", because they actually can travel one or two segments up or down the cord before synapsing. Lissauer's tract is the tract carrying these migrating axons, but they are only in the tract for a short time. Within one or two levels, they enter the dorsal horn and synapse. 

The dorsal horn is a multi-layered structure. The thin outermost layer is called the posterior marginalis layer. The wide pale second layer is called the substantia gelatinosa, and the layer deep to that is called the nucleus proprius. The layers continue into the ventral horn, but these are the three significant ones for now.

The two types of pain fibers enter different layers of the dorsal horn. Ad fibers enter the posterior marginalis and the nucleus proprius, and synapse on a second set of neurons. These are the secondary afferents (purple, below) which will carry the signal to the thalamus. The secondary afferents from both layers cross to the opposite side of the spinal cord and ascend in a tract called (logically) the spinothalamic tract. Tracts are always labeled from beginning to end.

The C fibers enter the substantia gelatinosa and synapse, but they do not synapse on secondary afferents. Instead they synapse on interneurons – neurons which do not project out of the immediate area. The interneurons must carry the signal to the secondary afferents in either the posterior marginalis or the nucleus proprius.

The spinothalamic tract ascends the entire length of the cord as shown above, and the entire brainstem, staying in about the same location all the way up. Below are representative slides showing the tract in the medulla and midbrain. Notice that by midbrain the spinothalamic tract appears to be continuous with the medial lemniscus. They will enter the VPL of the thalamus together.

 The spinothalamic system enters the VPL, synapses, and is finally carried to cortex by the thalamocortical neurons. Here is a schematic of the entire pathway:

E. Pain Control

It has been recognized for centuries that opium and related compounds (such as morphine) are powerful analgesics. Several decades ago scientists hunted down the opiate receptor which was responsible for the potent effects. They then reasoned that if there was such a receptor in the body, maybe the body used its own endogenous form of opium to control pain. (It has also been recognized for centuries that under certain circumstances, i.e. the heat of battle, a serious wound may not cause pain.) This hypothetical compound was named "endorphin", from endogenous-morphine. Soon after, an entire class of peptide neurotransmitters was discovered that interacted with the opiate receptor, and now includes endorphins, enkephalins, and dynorphins. Synthetic, exogenous forms of these compounds continue to be discovered, prescribed, and abused, and are classed under the general term, "narcotics".

There are opiate receptors throughout the central nervous system. In the dorsal horn, they are located on the terminals of the primary afferents, as well as on the cell bodies of the secondary afferents. Opiate interneurons in the spinal cord can be activated by descending projections from the brainstem (especially the raphe nuclei and periaqueductal grey), and can block pain transmission at two sites. 1) They can prevent the primary afferent from passing on its signal by blocking neurotransmitter release, and 2) they can inhibit the secondary afferent so it does not send the signal up the spinothalamic tract.

 F. The Proprioceptive System

The proprioceptive system arises from primarily the Aa afferents entering the spinal cord. These are the afferents from muscle spindles, Golgi tendon organs, and joint receptors. The axons travel for a little while with the discriminative touch system, in the posterior columns. Within a few segments, however, the proprioceptive information slips out of the dorsal white matter and synapses. After synapsing it ascends without crossing to the cerebellum.

Exactly where the axons synapse depends upon whether they originated in the legs or the arms. Leg fibers enter the cord at sacral or lumbar levels, ascend to the upper lumbar segments, and synapse in a medial nucleus called Clarke's nucleus (or nucleus dorsalis). The secondary afferents then enter the dorsal spinocerebellar tract on the lateral edge of the cord.

Fibers from the arm enter at cervical levels and ascend to the caudal medulla. Once there they synapse in a nucleus called the external cuneate (or lateral cuneate) nucleus, and the secondary axons join the leg information in the dorsal spinocerebellar tract.

The spinocerebellar tract stays on the lateral margin of the brainstem all the way up the medulla. Just before reaching the pons, it is joined by a large projection from the inferior olive. These axons together make up the bulk of the inferior cerebellar peduncle, which grows right out of the lateral medulla and enters the cerebellum.

 The figures above outline the course of the dorsal spinocerebellar tract. Surely, there must be a ventral spinocerebellar tract? Naturally, there is, and it travels in approximately the same place – the lateral margin of the spinal cord, just ventral to the dorsal spinocerebellar tract. The two cannot be distinguished in a normal myelin stain. The ventral spinocerebellar tract seems to defy the ipsilaterality of the cerebellum, because the fibers entering it in the spinal cord actually cross on their way into the tract. However, they (somewhat inefficiently) cross back before entering the cerebellum. Therefore the cerebellum still gets information from the ipsilateral body.

A note about generalizations:

There is actually a fair amount of mixing that goes on between the tracts. Some light touch information travels in the spinothalamic tract, so that lesioning the dorsal columns will not completely knock out touch and pressure sensation. Some proprioception also travels in the dorsal columns, and follows the medial lemniscus all the way to the cortex, so there is conscious awareness of body position and movement. The pain and temperature system, although it does ascend to somatosensory cortex, also has multiple targets in the brainstem and other areas.

For a more interactive tutorial on the anatomy, and for stunning three dimensional pictures of these pathways, try the Digital Anatomist in the "Other links" section.


Somatosensory Pathways From the Face

In the last section, we covered the three modalities of sensation from the body: discriminative touch, proprioception, and pain and temperature. These same modalities need to be addressed in the face as well, but sensory input from the face does not enter the spinal cord. In fact, it all enters the brainstem via the trigeminal nerve. Just as in the spinal cord, these three modalities have different receptors, travel along different tracts, and have different targets in the brainstem. Once the pathways synapse in the brainstem, they join the pathways from the body on their way up to the thalamus.

A. The Trigeminal Nucleus Complex

The collection of cells in the brainstem that can be called the trigeminal nucleus is huge – it stretches from midbrain to medulla. If we could see it in a transparent brainstem, it would look something like this:

Most of the sensory fibers enter the trigeminal ganglion, regardless of which trigeminal division they are coming from. Their cell bodies, like those of all somatosensory neurons, lie outside the CNS in the ganglion, and their proximal processes enter the brainstem in the mid-pons. From there they fan out to their different targets. Each modality will be described separately below.

B. Discriminative Touch

The large diameter (Ab) fibers enter directly into the main sensory nucleus of the trigeminal (V), also called the principal nucleus. Just like the somatosensory neurons of the body, they SYNAPSE, then CROSS. The secondary afferents can then join the medial lemniscus on its way to the thalamus.


C. Pain and Temperature

The small diameter fibers carrying pain and temperature enter at mid pons, and then do something unusual – they turn down the brainstem. They travel down the pons and medulla until they reach the caudal medulla, which is where they finally synapse and cross.

The tract that the descending axons travel in is called the spinal tract of V, and the long tail of a nucleus that they finally synapse in is called the spinal nucleus of V. These names come from the fact that they actually reach as far down as the upper cervical spinal cord. The spinal nucleus of V can be divided into three regions along its length; the region closest to the mouth is called subnucleus oralis, the middle region is called subnucleus interpolaris, and the region closest to the tail is called subnucleus caudalis. The pain fibers actually synapse in subnucleus caudalis, so you may hear that term used instead of the spinal nucleus of V.

 The secondary afferents from subnucleus caudalis cross to the opposite side, and join the spinothalamic tract on its way to the thalamus.

D. Proprioception

The proprioceptive axons in the trigeminal nerve are the stretch and tendon receptors from the muscles of mastication. (Recall that all of the muscles of facial expression are controlled by the facial nerve. ) These axons coming from the face have a strange characteristic unique among primary somatosensory neurons: their cell bodies are inside the CNS. They are the only exception to the rule. Although their cells look similar to cells in the dorsal root ganglion (the cell body does not come between the distal and proximal axon processes), they are located inside the brainstem in a nucleus called the mesencephalic nucleus. The mesencephalic nucleus is essentially a dorsal root ganglion that has been pushed into the CNS, so there are no synapses within it. The fibers enter the brainstem via a small branch of the trigeminal that bypasses the trigeminal ganglion, turn up towards the mesencephalic nucleus, pass by the cell body, and leave the nucleus immediately. Most then synapse in the nearby motor nucleus where they can initiate the stretch reflexes for the muscles of mastication. The stretch reflex in the face behaves exactly like that in the body, and tapping on the tendon of the masseter (for example) will produce a twitch.

 E. Motor Innervation

Motor or efferent control is not considered a sensory modality, but it is the fourth component of the extensive trigeminal complex. The motor nucleus of V lies just medial to the main sensory nucleus, and in it reside the a-motor neurons that control the muscles of mastication. The two principal muscles involved are the masseter (in your cheek) and the temporalis (over your temple), both of which tighten when you clench your teeth. The motor axons leave the mid-pons and bypass the trigeminal ganglion, and reach their targets via the mandibular division of the trigeminal nerve.


F. On to the Thalamus

The somatosensory information from the face joins that from the body and enters the thalamus with it. However, face information actually enters a different nucleus in the thalamus. Recall that information from the body enters the ventroposterior lateral nucleus (VPL). Information from the face actually enters the ventroposterior medial nucleus (VPM). The thalamocortical afferents take all of the signals, whether from VPL or VPM, to primary somatosensory cortex. Once there, it is distributed in a somatotopic (body-mapped) fashion, with the legs represented medially, at the top of the head, and the face represented laterally.


Spinal Motor Structures

A. The Spinal Cord

Although we usually study the spinal cord as a series of cross sections, it is important to remember that it is in fact a column, with continuous tracts and cell columns. However, the cord can be divided into segments by the nerve roots that come off of it; although the rootlets branch off nearly continuously, they coalesce into about 31 discrete nerves along the cord (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal nerves). At each segment, rootlets appear to come out of both the dorsal and ventral halves of the spinal cord, as you see here:

 In fact, only the ventral roots are coming out of the cord – the dorsal roots are actually going in. Throughout the cord, the dorsal grey matter (dorsal horns) deals with sensory perception, and receives information from the periphery through the dorsal root. The ventral horns contain the a-motor neurons, whose axons exit the cord via the ventral roots and travel directly to the muscles.

Along the dorsal root is a collection of cell bodies called the dorsal root ganglion. Inside the ganglion are the cell bodies of all the receptor neurons that send processes out to the periphery. The free nerve ending in the tip of your finger that feels the paper cut actually has its cell body back in the dorsal root ganglion. As you can see from the picture, the dorsal root ganglion is actually located ventrally, but you can tell that it is part of the dorsal root.

B. Levels of the Spinal Cord

By this time in the course you have probably noticed that different levels of the cord are different in shape. Could you identify the source of a section if you had nothing to compare it to? In general, you should be able to differentiate cervical from thoracic from lumbar from sacral. Here is a series of cross sections:

The first thing to notice is overall shape. Cervical sections tend to be wide and squashed looking, like an oval. Compare the cervical section to the round lumbar section.

 The second thing to check for is a ventral horn enlargement. At segments that control a limb, the motor neurons are large and numerous. This causes enlarged ventral horns in two places: the lower cervical sections (C5-C8) and the lumbar/sacral sections. If you see an enlargement, you just need to differentiate cervical from lumbar. This can be done by shape (see above) or by proportion of white matter.

The amount of white matter relative to grey matter decreases as you move down the cord. This is logical – in the white matter of the cervical cord you have all of the axons going to or from the entire body, more or less. In sacral cord the white matter contains only those axons going to or from the last couple of dermatomes – all other axons have "gotten off" at higher levels. This is why sacral cord looks like it has so much grey matter – really it has just lost all of the white.

So, in summary, here are the level cues so far: wide flat cord, lots of white matter, ventral horn enlargements = cervical. Round cord, ventral horn enlargements = lumbar. Small round cord, almost no white matter = sacral. And the remaining level, thoracic, is the easiest of all. Notice the pointed tips which stick out between the small dorsal and ventral horns. This extra cell column is called the intermediate horn, or the intermediolateral cell column. It is the source of all of the sympathetics in the body, and occurs only in thoracic sections.

C. Muscle Spindles and the Myotatic Reflex

One of the most familiar reflexes is the stretch reflex, also known as the knee-jerk reflex and the myotatic reflex. In its simplest form it is a 2-neuron loop, one afferent neuron and one efferent neuron. The afferent neuron is connected to a muscle spindle, which detects stretch in the muscle. The efferent neuron is the motor neuron, which causes the muscle to twitch.

But there are actually several types of afferents reporting on the status of the muscle. Let's look more closely at the muscle spindle:

The muscle spindle is a small group of muscle fibers walled off from the rest of the muscle by a collagen sheath. The sheath has a spindle or "fusiform" shape, so these fibers are called intrafusal fibers, and are contrasted with the extrafusal fibers, which are the power-generating muscle fibers. There are two types of nerve endings wrapped around this intrafusal fiber, both of which monitor its degree of stretch – as the muscle stretches, so does this capsule within it. These two stretch receptors are sensitive to different time scales, however. The first is called a Ia (that's one-A) fiber; the classification scheme is based on diameter and conduction velocity, so the Ia's are the largest and fastest. The Ia fiber fires like crazy when the muscle is stretching, but it is rapidly adapting. As soon as the muscle stops changing length, and holds a new position, the Ia adapts to the new length and stops firing. But you also need to know the position of your muscle when it is still. The second type of stretch receptor is called a II fiber, and it is slowly adapting. It also responds when the muscle is stretching, but it maintains a firing rate after the muscle has stopped moving (essentially, it is non-adapting). This information is part of what allows you to tell the position of your arm when your eyes are closed.

Rule of nomenclature – if there is a Ia, where is Ib? The Ib fibers are not connected to muscle spindles at all. Instead they are embedded in the tendon, and monitor overall muscle tension from there. They are also called Golgi tendon organs (the word "Golgi" is littered throughout neuroanatomy – he was a famous early anatomist).

Now, there is a potential problem with the muscle spindle system which may have occurred to you. What happens when the muscle gets shorter? Does the spindle go limp and slack? How can it remain sensitive to stretch at short lengths? This is where the intrafusal fiber comes into play. Like any muscle fiber, it can contract. When it contracts, the entire spindle shortens, remaining taut, and the sensitivity is intact. There are small motor neurons in the ventral horn that innervate the intrafusal muscle fibers and cause them to contract – they are the g-motor neurons. These neurons are excited every time the a-motor neurons fire, so that as the muscle contracts, the intrafusals contract with it.

How are they all hooked together? There are two simple rules:

1. When the stretch receptors fire, the a-motor neuron is excited, and the muscle contracts.

2. When the Golgi tendon organ fires, the a-motor neuron is inhibited (via an inhibitory interneuron), and the muscle relaxes.

The purpose here is that the stretch receptors tell the muscle when it needs a little more force – that despite intending to contract the muscle is lengthening. This helps you to maintain the correct muscle tone. The Golgi tendon organs, on the other hand, begin to fire when the tension on the tendon is so great that you are in danger of injury. They have a protective function, and therefore they tell the muscle to ease off before it tears. 

Occasionally, especially in cases of pyramidal tract damage, these two systems can get stuck in a loop, where they alternately trigger each other, causing the muscle to contract-relax-contract-relax, several times a second. This rapid trembling is called clonus, and can be a sign of pathology or extreme muscle fatigue.

D. Multiple Motor Pathways in the Cord

There are several pathways which innervate the a-motor neurons. They can be roughly grouped into the voluntary motion pathways and the postural pathways. The voluntary pathways include the lateral and anterior corticospinal systems, as covered in the "Basic motor" section. The postural pathways do not originate in cortex; instead their function is to maintain an upright posture against gravity, a task which requires hundreds of little muscular adjustments that we are not aware of. There are three principal pathways in humans: the vestibulospinal, tectospinal, and reticulospinal pathways. Pathways are always named beginning-to-end, so these originate in the vestibular nuclei, tectum (superior colliculi), and reticular formation, respectively. The rubrospinal system (from the red nucleus) is also sometimes included, but in humans it may be insignificant. 

Although these pathways do not originate in cortex, they are controlled to some degree by cortical structures. You must be able to turn off selective postural systems to accomplish other movements. This becomes apparent when the cortex is damaged or cut off from the postural pathways, and can no longer control them. If the cortical input is damaged close to its source, (i.e., in the internal capsule), the result is what is called a decorticate posture. Here the postural pathways flex the upper limbs and extend the lower limbs by default, since they are getting no input from cortex.

If the damage cuts off not just cortical input but all input from the entire cerebrum, such as with a massive brainstem injury, the result is a decerebrate posture. In the decerebrate position all four limbs are extended and somewhat turned in (pronated). This sort of injury is much more serious than an injury of the internal capsule; the prognosis is usually very poor.

E. Injury to the Corticospinal Tract

Just as the postural pathways have a "mind of their own" when cortical control is cut off, the spine can also produce some weird behaviors when the corticospinal tract is damaged. All of the spinal reflexes are local – all of the cells involved are contained within one or two segments, and cortex is not necessary. Therefore reflexes would still be present in a transected spinal cord. However, the cortex normally keeps a tight rein on reflexive behavior, so that it doesn't interfere with normal movements. When the cortex is cut off, the spinal cord becomes hyperreflexic. All of the normal reflexes become exaggerated, and some new ones appear. For example, stroking the lateral sole of your foot with a sharp object would normally make your toes curl downward. In a patient with corticospinal damage (also called upper motor neuron damage), the big toe would lift up and the toes would fan out. This is called the Babinski sign, and it is always pathological (with the exception of very young infants).


Brainstem Nuclei of Cranial Nerves

A. The Cranial Nerves

The cranial nerves (with the exception of I and II) originate in the brainstem, which includes the midbrain, the pons, and the medulla. The 12 cranial nerves can be divided into sensory, motor, or mixed nerves. Overall, sensory nerve nuclei tend to be located in the lateral brainstem, while motor nuclei tend to be located medially. Nerves with mixed sensory and motor fibers must have more than one nucleus of origin – at least one sensory (afferent) and one motor (efferent). Sometimes more than one nerve will originate from a single nucleus: for example, the sense of taste is spread across at least two nerves but merges into a single nucleus. Finally, keep in mind that any sensory nucleus is receiving input from the periphery, but the sensory receptor cell bodies are never in the nucleus itself. They will always be located just outside the CNS in a ganglion.

Here is a dorsal view of the brainstem, looking down through it as though it were transparent, so you can see the relative positions of the cranial nerve nuclei. Motor or efferent nuclei are blue, sensory or afferent nuclei are yellow. Note that this is a schematic to give you the big picture – some of these nuclei would technically overlap if you could really see through the brainstem.

Abbreviations: EW: Edinger-Westphal nuc. III: oculomotor nuc. IV: trochlear nuc. meV: mesencephalic nuc. of V V: trigeminal moV: motor nuc. of V senV: main sensory nuc. of V spV: spinal nuc. of V VI: abducens nuc. VII: facial nuc. VIIIc: cochlear nuc. VIIIv: vestibular nuc. IX: glossopharyngeal X: vagus amb: nuc. ambiguus dnv: dorsal nuc. of the vagus sol: solitary nucleus
XII: hypoglossal nuc.

Not shown: -cranial nerve I -cranial nerve II -cranial nerve XI
-salivatory nuclei

The next sections describe the functions and features of the nerves and nuclei, with highlighted pictures to accompany the text. HOWEVER, these pictures were taken from the student collections of microscope slides at Washington University, and as such are not always ideal images of the nuclei. The purpose of this section is to lay down a conceptual framework of the cranial nerves. For larger, clickable & quizzable anatomy images, please use a specialized neuroanatomy program, such as the Digital Anatomist listed in the "Other Links" section.

B. Nerves that Innervate the Eye Muscles

Nerves III, IV, and VI are pure motor nerves that innervate the extrinsic eye muscles. All are located very close to the midline.

III – The Oculomotor Nerve

This nerve innervates the bulk of the eye muscles: superior and inferior recti, medial rectus, and inferior oblique. If this nerve is damaged, the action of the remaining two muscles (superior oblique and lateral rectus) pulls the eye "down and out". The nucleus is located medially in the midbrain, and the nerve fibers exit ventrally, just inside the peduncles.


Edinger Westphal Nucleus

This nucleus is the source of the parasympathetics to the eye, which constrict the pupil and accommodate the lens. It is located just inside the oculomotor nuclei, like nested "V"s. The fibers travel in the IIIrd nerve, so damage to that nerve will also produce a dilated pupil.

Note: the eye drops that you are given at the ophthomologist's office are an acetylcholine antagonist (blocker) so they inhibit the actions of the parasympathetic system. As a result your eyes are dilated, so the physician can look inside clearly. As a side effect, you cannot accommodate your lens (focus on close objects) which is why you can't read while you are sitting in the waiting room.

IV – The Trochlear Nerve

"Trochlea" is from the Latin word for pulley. If you remember from gross anatomy, the superior oblique muscle loops through a pulley-like sling on its way to the back of the eye. Hence the IVth nerve innervates the superior oblique. This nucleus is also located near the midline. It is very small, and hard to find in sections. It looks like a crescent-notch taken out of a dark fiber bundle in the rostral pons. The fiber bundle is the MLF, which carries eye movement signals between brainstem nuclei. 

The trochlear nerve is unique for two reasons: 1) it exits the brainstem dorsally, and 2) it crosses on the way out. The fibers cross over each other just like a half-tied shoelace in the roof of the fourth ventricle.


VI – The Abducens Nerve

"Abducens" comes from "abduct". To abduct a part is generally to move it laterally, and the muscle that abducts the eye is the lateral rectus. It is the only muscle innervated by VI. The nucleus is again near the midline, but this one is in the pons. The key landmark for finding the abducens is actually the facial nerve. The facial nerve fibers come up to the floor of the fourth ventricle, loop around in a hairpin turn, and dive back into the pons. The bump that they loop over is the abducens nucleus.

The abducens fibers exit the pons medially and ventrally. Often you can see the facial fibers exiting in the same section; the facial fibers will always be lateral.


C. The Trigeminal Nerve

All sensation from the face and mouth is covered by the mixed trigeminal nerve. A branch of the trigeminal is injected by your dentist when you have a cavity filled. The trigeminal also carries motor fibers to the muscles of mastication (chewing). The most prominent of these is the masseter muscle, the hard knot in your cheek when you clench your teeth. The functions of the different trigeminal nuclei are extensively covered in the "Somatosensory pathways from the face" section, so they will not be repeated here.

The mesencephalic nucleus is a thin ribbon of cells that runs along the fourth ventricle and cerebral aqueduct, just outside the periaqueductal grey.


The motor nucleus is located in the mid-pons, and is often hard to see. The best landmark is the presence of trigeminal nerve fibers streaking through the adjacent middle cerebellar peduncles (MCP). The fibers appear as a hand gripping a pale egg. The pale egg is the motor nucleus.

Once you have found the motor nucleus, look immediately lateral to find the main sensory nucleus. It is a faint collection of cells tucked just inside the middle cerebellar peduncle.

The spinal nucleus of V is easiest to see in the caudal medulla, although it extends throughout the entire medulla. Here it bears some resemblance to the dorsal horn of the spinal cord, both functionally and anatomically. Just like the dorsal horn, it receives pain afferents. The adjacent spinal tract of V is analogous to Lissauer's tract, as it is carrying those same pain afferents before they synapse.


D. The Facial Nerve

All of the muscles of facial expression are innervated by the facial nerve. It is considered a mixed cranial nerve, however, since it also carries the sensation of taste. The facial nerve also carries some parasympathetic fibers to the salivary glands.

Recall that the facial nerve fibers loop over the abducens nucleus in the pons. The facial nucleus itself is hard to see in a myelin stain. The fibers of the facial nerve do not acquire their myelin (and become dark) until they arrive at the hairpin turn, so you cannot even trace them back to the nucleus. The approximate location is shown below, however.


E. Taste

Taste fibers, from the taste buds, are predominantly (from the front 2/3 of the tongue, anyway) carried by the facial nerve. (Keep in mind that touch and pain sensation from the tongue is V, and motor to the tongue is XII.) Taste from the back of the tongue and palate is carried by the glossopharyngeal nerve. Regardless of their origin, the taste fibers enter the solitary tract of the medulla, and synapse in the surrounding solitary nucleus.

Taste and touch sensation at the back of the throat are carried by the glossopharyngeal nerve, and also synapse in the solitary nucleus. These sensations can trigger the gag reflex.

F. Hearing and Balance

The VIIIth nerve carries auditory information from the cochlea and vestibular information from the semicircular canals, utricle, and saccule. It is really two nerves running together, the auditory (cochlear) nerve and the vestibular nerve. The VIIIth nerve is very important clinically because a common type of tumor, the acoustic neuroma, can arise from the nerve as it exits the brainstem.

The cochlear nuclei are like small hands draped over the inferior cerebellar peduncles (ICP), and are fairly small in primates. The vestibular nuclei have several subdivisions, however, and extend throughout a large fraction of the pons. 

G. The Glossopharyngeal Nerve

The IXth nerve has no real nucleus to itself. Instead it shares nuclei with VII and X. The sensory information in IX goes to the solitary nucleus, a nucleus it shares with VII and X. All motor information, essentially the innervation of the stylopharyngeus muscle, comes from the nucleus ambiguus, also shared with X. Finally, like VII, there are some parasympathetic fibers in IX that innervate the salivary glands.

H. Salivation

The salivation center is a pair of nuclei located just rostral to the dorsal nucleus of the vagus, the superior and inferior salivatory nuclei. They supply the parasympathetic innervation of the various salivary glands, and send their axons through the facial and glossopharyngeal nerves.

I. The Various and Sundry Nuclei of the Vagus

When you think vagus, you tend to think parasympathetic – this is a flashback to your gross anatomy days. However, the vagus has dozens of functions. They can be grouped into about three categories, and each category is associated with a medullary nucleus. The first is the nucleus ambiguus, which is a motor nucleus. Cells in the nucleus ambiguus are very difficult to see (hence the name), and innervate striated muscle throughout the neck and thorax. This includes some muscles of the palate and pharynx, muscles of the larynx, and the parasympathetic innervation of the heart. Problems with the vagus can show up as hoarseness, or a deviated uvula: X elevates the palate when you open up and say "AH". An asymmetrical uvula would indicate that X is not working on one side.

The second is the dorsal nucleus of the vagus, which is the secretomotor parasympathetic nucleus. Secretomotor primarily means that it stimulates glands – including mucus glands of the pharynx, lungs, and gut, as well as gastric glands in the stomach. (Incidentally, it is fair-inks, not far-nicks.)

The third is the sensory nucleus of the vagus, the solitary nucleus. As we have seen, it receives taste information, sensation from the back of the throat, and also visceral sensation. Visceral sensation includes blood pressure receptors, blood-oxygen receptors, sensation in the larynx and trachea, and stretch receptors in the gut. 

J. The Spinal Accessory Nerve

The XIth nerve actually originates in the cervical spinal cord. Were it not for the fact that it sneaks up along side the medulla and exits the skull with IX and X, it might not even be a cranial nerve. It is a motor nerve that innervates two muscles: the trapezius and the sternocleidomastoid.

K. The Hypoglossal Nerve

The XIIth nerve innervates the muscles of the tongue. Like most pure motor nuclei, the XII nucleus is located along the midline, and can be found throughout most of medulla. The tongue muscles actually push the tongue forward, so a problem with the hypoglossal nerve can be detected by asking the patient to stick out his tongue. The tongue will deviate towards the weak side, towards the side of the lesion.




Basal Ganglia and Cerebellum

The basal ganglia and cerebellum are large collections of nuclei that modify movement on a minute-to-minute basis. Motor cortex sends information to both, and both structures send information right back to cortex via the thalamus. (Remember, to get to cortex you must go through thalamus.) The output of the cerebellum is excitatory, while the basal ganglia are inhibitory. The balance between these two systems allows for smooth, coordinated movement, and a disturbance in either system will show up as movement disorders.

A. The Basal Ganglia

What are the basal ganglia? The name is confusing, as generally a ganglion is a collection of cell bodies outside the central nervous system. Blame the early anatomists. The basal ganglia are a collection of nuclei deep to the white matter of cerebral cortex. The name includes: caudate, putamen, nucleus accumbens, globus pallidus, substantia nigra, subthalamic nucleus, and historically the claustrum and the amygdala. However, the claustrum and the amygdala do not really deal with movement, nor are they interconnected with the rest of the basal ganglia, so they have been dropped from this section. Other groupings you may hear are the striatum (caudate + putamen + nucleus accumbens), the corpus striatum (striatum + globus pallidus), or the lenticular nucleus (putamen + globus pallidus), but these groupings obviously get confusing very quickly, so we will try to avoid them.

The anatomy of these structures should be a review from the "coronal and horizontal sections" lab. Here once again are the basal ganglia as they appear when stained for myelin:

rostral section: 


middle section:


caudal section:

An alternate stain is the acetylcholinesterase (AChE) stain. This technique stains for the enzyme that degrades acetylcholine (ACh), a major neurotransmitter. Areas which use ACh generally stain darkly. Here is a section through monkey brain, stained for AChE.

 You can see that the caudate and putamen are stained, while the globus pallidus remains fairly pale. This emphasizes their different functions and connections. And those are...?

B. Different Functions and Connections

The relationships between the nuclei of the basal ganglia are by no means completely understood. When dealing with the brain, you may sometimes be tempted to think that everything is connected to everything else. Take heart, some fairly simple generalizations and schematics can be drawn.

The caudate and putamen receive most of the input from cerebral cortex; in this sense they are the doorway into the basal ganglia. There are some regional differences: for example, medial caudate and nucleus accumbens receive their input from frontal cortex and limbic areas, and are implicated more in thinking and schizophrenia than in moving and motion disorders. The caudate and putamen are reciprocally interconnected with the substantia nigra, but send most of their output to the globus pallidus (see diagram below).

The substantia nigra can be divided into two parts: the substantia nigra pars compacta (SNpc) and the substantia nigra pars reticulata (SNpr). The SNpc receives input from the caudate and putamen, and sends information right back. The SNpr also receives input from the caudate and putamen, but sends it outside the basal ganglia to control head and eye movements. The SNpc is the more famous of the two, as it produces dopamine, which is critical for normal movement. The SNpc degenerates in Parkinson's disease, but the condition can be treated by giving oral dopamine precursors.

The globus pallidus can also be divided into two parts: the globus pallidus externa (GPe) and the globus pallidus interna (GPi). Both receive input from the caudate and putamen, and both are in communication with the subthalamic nucleus. It is the GPi, however, that sends the major inhibitory output from the basal ganglia back to thalamus. The GPi also sends a few projections to an area of midbrain (the PPPA), presumably to assist in postural control.

This schematic summarizes the connections of the basal ganglia as described above.

 Although there are many different neurotransmitters used within the basal ganglia (principally ACh, GABA, and dopamine), the overall effect on thalamus is inhibitory. The function of the basal ganglia is often described in terms of a "brake hypothesis". To sit still, you must put the brakes on all movements except those reflexes that maintain an upright posture. To move, you must apply a brake to some postural reflexes, and release the brake on voluntary movement. In such a complicated system, it is apparent that small disturbances can throw the whole system out of whack, often in unpredictable ways. The deficits tend to fall into one of two categories: the presence of extraneous unwanted movements or an absence or difficulty with intended movements.

C. Lesions of the Basal Ganglia

Lesions in specific nuclei tend to produce characteristic deficits. One well-known disorder is Parkinson's disease, which is the slow and steady loss of dopaminergic neurons in SNpc. An instant Parkinson-like syndrome will result if these neurons are damaged. This happened several years ago to an unfortunate group of people who took some home-brewed Demerol in search of a high. It was contaminated by a very nasty byproduct, MPTP ,which selectively zapped the SNpc neurons. The three symptoms usually associated with Parkinson's are tremor, rigidity, and bradykinesia. The tremor is most apparent at rest. Rigidity is a result of simultaneous contraction of flexors and extensors, which tends to lock up the limbs. Bradykinesia, or "slow movement", is a difficulty initiating voluntary movement, as though the brake cannot be released.

Huntington's disease, or chorea, is a hereditary disease of unwanted movements. It results from degeneration of the caudate and putamen, and produces continuous dance-like movements of the face and limbs. A related disorder is hemiballismus, flailing movements of one arm and leg, which is caused by damage (i.e., stroke) of the subthalamic nucleus.

D. The Cerebellum

The cerebellum is involved in the coordination of movement. A simple way to look at its purpose is that it compares what you thought you were going to do (according to motor cortex) with what is actually happening down in the limbs (according to proprioceptive feedback), and corrects the movement if there is a problem. The cerebellum is also partly responsible for motor learning, such as riding a bicycle. Unlike the cerebrum, which works entirely on a contralateral basis, the cerebellum works ipsilaterally.

The cerebellum ("little brain") has convolutions similar to those of cerebral cortex, only the folds are much smaller. Like the cerebrum, the cerebellum has an outer cortex, an inner white matter, and deep nuclei below the white matter.

Cat cerebellum, sagittal section

Single folium, enlarged

 If we enlarge a single fold of cerebellum, or a folium, we can begin to see the organization of cell types. The outermost layer of the cortex is called the molecular layer, and is nearly cell-free. Instead it is occupied mostly by axons and dendrites. The layer below that is a monolayer of large cells called Purkinje cells, central players in the circuitry of the cerebellum. Below the Purkinje cells is a dense layer of tiny neurons called granule cells. Finally, in the center of each folium is the white matter, all of the axons traveling into and out of the folia.

These cell types are hooked together in stereotypical ways throughout the cerebellum.

 Mossy fibers are one of two main sources of input to the cerebellar cortex. A mossy fiber is an axon terminal that ends in a large, bulbous swelling. These mossy fibers enter the granule cell layer and synapse on the dendrites of granule cells (right); in fact the granule cells reach out with little "claws" to grasp the terminals. The granule cells then send their axons up to the molecular layer, where they end in a T and run parallel to the surface. For this reason these axons are called parallel fibers. The parallel fibers synapse on the huge dendritic arrays of the Purkinje cells.

However, the individual parallel fibers are not a strong drive to the Purkinje cells. The Purkinje cell dendrites fan out within a plane, like the splayed fingers of one hand. If you were to turn a Purkinje cell to the side, it would have almost no width at all. The parallel fibers run perpendicular to the Purkinje cells, so that they only make contact once as they pass through the dendrites.

Although each parallel fiber touches each Purkinje cell only once, the thousands of parallel fibers working together can drive the Purkinje cells to fire like mad.

The second main type of input to the folium is the climbing fiber. The climbing fibers go straight to the Purkinje cell layer and snake up the Purkinje dendrites, like ivy climbing a trellis. Each climbing fiber associates with only one Purkinje cell, but when the climbing fiber fires, it provokes a large response in the Purkinje cell.

The Purkinje cell (left) compares and processes the varying inputs it gets, and finally sends its own axons out through the white matter and down to the deep nuclei. Although the inhibitory Purkinje cells are the main output of the cerebellar cortex, the output from the cerebellum as a whole comes from the deep nuclei. The three deep nuclei are responsible for sending excitatory output back to the thalamus, as well as to postural and vestibular centers. There are a few other cell types in cerebellar cortex, which can all be lumped into the category of inhibitory interneuron. The Golgi cell is found among the granule cells. The stellate and basket cells live in the molecular layer. The basket cell (right) drops axon branches down into the Purkinje cell layer where the branches wrap around the cell bodies like baskets.

E. Inputs and Outputs of the Cerebellum

The cerebellum operates in 3's: there are 3 highways leading in and out of the cerebellum, there are 3 main inputs, and there are 3 main outputs from 3 deep nuclei. They are:

The 3 highways are the peduncles, or "stalks". There are 3 pairs: the inferior, middle, and superior peduncles.

The 3 inputs are: Mossy fibers from the spinocerebellar pathways, climbing fibers from the inferior olive, and more mossy fibers from the pons, which are carrying information from cerebral cortex. The mossy fibers from the spinal cord have come up ipsilaterally, so they do not need to cross. The fibers coming down from cerebral cortex, however, DO need to cross (remember the cerebrum is concerned with the opposite side of the body, unlike the cerebellum). These fibers synapse in the pons (hence the huge block of fibers in the cerebral peduncles labeled "corticopontine"), cross, and enter the cerebellum as mossy fibers.

The 3 deep nuclei are the fastigial, interposed, and dentate nuclei. The fastigial nucleus is primarily concerned with balance, and sends information mainly to vestibular and reticular nuclei. The dentate and interposed nuclei are concerned more with voluntary movement, and send axons mainly to thalamus and the red nucleus.




Hypothalamus and Autonomic Nervous System

A. Hypothalamus = Homeostasis

The main function of the hypothalamus is homeostasis, or maintaining the body's status quo. Factors such as blood pressure, body temperature, fluid and electrolyte balance, and body weight are held to a precise value called the set-point. Although this set-point can migrate over time, from day to day it is remarkably fixed.

To achieve this task, the hypothalamus must receive inputs about the state of the body, and must be able to initiate compensatory changes if anything drifts out of whack. The inputs include:

Nucleus of the solitary tract – this nucleus collects all of the visceral sensory information from the vagus and relays it to the hypothalamus and other targets. Information includes blood pressure and gut distension.

Reticular formation – this catchall nucleus in the brainstem receives a variety of inputs from the spinal cord. Among them is information about skin temperature, which is relayed to the hypothalamus.

Retina – some fibers from the optic nerve go directly to a small nucleus within the hypothalamus called the suprachiasmatic nucleus. This nucleus regulates circadian rhythms, and couples the rhythms to the light/dark cycles.

Circumventricular organs – these nuclei are located along the ventricles, and are unique in the brain in that they lack a blood-brain barrier. This allows them to monitor substances in the blood that would normally be shielded from neural tissue. Examples are the OVLT, which is sensitive to changes in osmolarity, and the area postrema, which is sensitive to toxins in the blood and can induce vomiting. Both of these project to the hypothalamus.

Limbic and olfactory systems – structures such as the amygdala, the hippocampus, and the olfactory cortex project to the hypothalamus, and probably help to regulate behaviors such as eating and reproduction.

The hypothalamus also has some intrinsic receptors, including thermoreceptors and osmoreceptors to monitor temperature and ionic balance, respectively.

Once the hypothalamus is aware of a problem, how does it fix it? Essentially, there are two main outputs:

Neural signals to the autonomic system – the (lateral) hypothalamus projects to the (lateral) medulla, where the cells that drive the autonomic systems are located. These include the parasympathetic vagal nuclei and a group of cells that descend to the sympathetic system in the spinal cord. With access to these systems, the hypothalamus can control heart rate, vasoconstriction, digestion, sweating, etc.

Endocrine signals to/through the pituitary – recall that an endocrine signal is a chemical signal sent via the bloodstream. Large hypothalamic cells around the third ventricle send their axons directly to the posterior pituitary, where the axon terminals release oxytocin and vasopressin into the bloodstream. Smaller cells in the same area send their axons only as far as the base of the pituitary, where they empty releasing factors into the capillary system of the anterior pituitary. These releasing factors induce the anterior pituitary to secrete any one of at least six hormones, including ACTH and thyroid-stimulating hormone (TSH).

Ultimately the hypothalamus can control every endocrine gland in the body, and alter blood pressure (through vasopressin and vasoconstriction), body temperature, metabolism (through TSH), and adrenaline levels (through ACTH).

 In the news lately: The hypothalamus controls body weight and appetite, but it is not entirely clear how. Sensory inputs, including taste, smell, and gut distension, all tell the hypothalamus if we are hungry, full, or smelling a steak. Yet it is mysterious how we are able to vary our eating habits day to day and yet maintain about the same weight (sometimes despite all efforts to the contrary!) . The "set-point" theory is an old one in diet science, but until recently the mechanics of maintaining that set point were unknown. It appears that there is an endocrine component to the appetite system. Recent studies in mice have shown that the fat cells of normal overfed mice will release a protein called leptin (or OB, after the gene name), which reduces appetite and perks up metabolism. Leptin is presumably acting on the hypothalamus. Underfed mice, on the other hand, produce little or no leptin, and they experience an increase in appetite and a decrease in metabolism. In both of these mice, the result is a return to normal weight. But what would happen if a mouse (or human) had a defective OB gene? Weight gain would never trigger fat cells to release leptin, the hypothalamus would never slow the appetite or increase metabolism, and the mouse would slowly but surely become obese (how the gene got its name). Sure enough, shortly after these experiments hit the news, the human OB gene was discovered and a few obese patients were found to have the mutation. Many more obese patients had normal OB genes, however, indicating that there is much more to the story yet to be discovered.

B. The Anatomy of the Hypothalamus

The hypothalamus, as you would expect from the name, is located below the thalamus on either side of the third ventricle. These sections have been cut coronally, and show only one side of the hypothalamus.

In this anterior section through hypothalamus, you can see the large neurons of the paraven-tricular nucleus, which send axons to the posterior pituitary. The cells in the periventricular zone send axons to the median eminence, from which releasing factors are carried to the anterior pituitary.

The nucleus basalis is a cholinergic nucleus involved in sleep and wakefulness.

This section is posterior to the first. The hypothalamic nuclei are hard to distinguish, but the arrows point out approximate locations. The pituitary stalk would normally be continuous with the median eminence, but it is a fragile structure usually lost in dissection. 

Note the fornix descending through the hypothalamus. The fornix originates in the hippo-campus and ends in the mammillary bodies.

In this posterior section you can see the fornix joining the mammillary body. This is also a nice section to demonstrate the way that the internal capsule fibers flow into the cerebral peduncle.

C. The Autonomic Nervous System

The autonomic nervous system is an entire little brain unto itself; its name comes from "autonomous", and it runs bodily functions without our awareness or control. It is divided into two systems which, where they act together, often oppose each other: the sympathetic and parasympathetic systems. The sympathetic system evokes responses characteristic of the "fight-or-flight" response: pupils dilate, muscle vasculature dilates, the heart rate increases, and the digestive system is put on hold. The parasympathetic system has many specific functions, including slowing the heart, constricting the pupils, stimulating the gut and salivary glands, and other responses that are not a priority when being "chased by a tiger". The state of the body at any given time represents a balance between these two systems.

The best way to learn the functions and structures of each system is by comparison. The following table lists some attributes of each:

The Parasympathetic System The Sympathetic System

Origins: Parasympathetic cells are located in different nuclei throughout the brainstem, as well as a few in the sacral spinal cord. Their axons travel to the target organ, synapse in ganglia in or near the organ wall, and finally innervate the organ as "post-ganglionics". Examples of these ganglia include the ciliary, otic, and pterygopalatine ganglia in the head, and diffuse networks of cells in the walls of the heart, gut, and bladder.


Nuclei of origin:

Edinger- Westphal nucleus - Axons from this nucleus travel with cranial nerve III and have 2 functions: – pupil constriction
- lens accommodation

Salivatory nuclei – These nuclei in the medulla send axons to the salivary glands via the VIIth and IXth nerves.

Dorsal nucleus of the vagus – This nucleus gives rise to the secretomotor fibers of the vagus nerve (X). Its functions include: – stimulate gastric secretion – stimulate gut motility
- stimulate respiratory secretions

Nucleus ambiguus (and surrounding cells) – Axons from these cells project via the vagus to the heart, lungs, and pharynx. Functions include: – decrease heart rate
- bronchial constriction

The cells of the intermediolateral column in the thoracic spinal cord are the source of all the sympathetics. They also travel to ganglia before reaching the target organ, but the sympathetic ganglia are often far from the target.


Some notable ganglia: 

Superior cervical ganglion – supplies sympathetics to the head, including those that: – dilate the pupils – stimulate sweat glands – lift the eyelids

Celiac and mesenteric ganglia – These ganglia distribute sympathetics to the gut. Functions include: – vasoconstriction – inhibition of secretions

Chain ganglia running along the spinal cord distribute sympathetics to the thorax and periphery to: – increase heart rate – dilate bronchi – selectively vasoconstrict
- vasodilate in active muscles

 The autonomic system also receives afferents that carry information about the internal organs. They return to separate locations:

Parasympathetic afferents

Nearly all of the afferents return via the vagus to a single nucleus, the nucleus of the solitary tract. Like all sensory afferents, the actual cell bodies of the neurons sit just outside the CNS in a ganglion (the nodose ganglion). The central processes of the neurons enter the medulla in the solitary tract and travel a bit before synapsing in the surrounding nucleus of the solitary tract. The solitary tract is somewhat analogous to Lissauer's tract in the spinal cord.

The nucleus receives information about blood pressure, carbon dioxide levels, gut distention, etc. 

Sympathetic afferents

Afferents reenter the dorsal horn of the spinal cord along side of the sensory afferents from the skin. The sympathetic afferents mainly carry information about visceral pain. Since this information converges with pain from the body surface, the pain is often perceived as originating at the body surface instead of deep in the viscera. This phenomenon is called referred pain, and follows predictable patterns. For example, afferents from the heart enter the spinal cord at the same level as those from the shoulder region. This is why pain in the heart (a heart attack) is often referred to the shoulder.


D. The Baroreceptor Reflex

A reflex is a pathway with an afferent signal (sensory) that evokes an efferent response (motor). The most common example is the stretch reflex, or knee-jerk reflex. A quick stretch of the tendon causes a brief contraction of the muscle. The autonomic system has several similar reflexes. One of these is the baroreceptor reflex, which maintains a constant blood pressure despite standing up or lying down.

The afferent signal comes from baroreceptors in the carotid sinus, a swelling of the carotid artery in the neck. If blood pressure suddenly jumps up, the baroreceptors respond and send the signal back to the nucleus of the solitary tract (NTS). Neurons in the NTS project to an adjacent vagal nucleus, the nucleus ambiguus, and excite the neurons that project to the heart. These acetylcholinergic neurons slow the heart, bringing down the blood pressure a little.

However, there is more to the story. In the knee-jerk reflex, for the quadriceps muscle to contract briefly, the hamstring muscle must also relax briefly. As a flexor-extensor pair, they must always receive opposite signals. The sympathetic and parasympathetic systems are like a flexor-extensor pair, so when activating the parasympathetic you must inhibit the sympathetic. Just like in the spinal cord, this is accomplished by an inhibitory interneuron.

When the high blood pressure signal arrives at the NTS, an inhibitory interneuron projects to the group of cells that control the sympathetic neurons in thoracic cord. These cells are called the descending sympathetics. An important feature of the descending sympathetics is that they are constantly firing at a steady level. This enables them to be turned down – if a neuron was already silent, an inhibitory signal would make no difference. Therefore, in response to the surge in blood pressure, the descending sympathetics are inhibited, and the sympathetics in the spinal cord fire at a much lower rate. As a result, the heart and the blood vessels are allowed to relax, the heart slows, vasodilation occurs, and blood pressure drops. The inhibition of the sympathetic system is actually a more powerful way to lower blood pressure than activating the parasympathetic system.



Medial Temporal Lobe and Memory

On the medial surface of the temporal lobe are three structures critical for normal human functioning. From rostral to caudal, they are the olfactory cortex, the amygdala, and the hippocampus. We will look at the anatomy and function of each separately, although they are often grouped together as "the limbic system".

A. The Olfactory System

The olfactory system actually begins in the roof of the nasal cavity. The olfactory receptors are ciliated epithelial cells with an array of receptors capable of detecting thousands of different odors.

 However, just as with any sensory system, the receptor neurons themselves do not project to the cerebral hemispheres. Their axons project up through the cribiform plate of the skull to synapse on the dendrites of the mitral cells of the olfactory bulb. The axons of the olfactory receptors make up the elusive cranial nerve I. This fragile tract is susceptible to shearing forces in head trauma, and loss of smell is a surprisingly debilitating injury.

Here is an example of a section through olfactory bulb. The olfactory bulb is not a simple relay (something which passively transmits the signal), but is a sophisticated structure in itself. The mitral cell- olfactory neuron synapse is actually within a tangle of axons and dendrites that is called a glomerulus. There is a second cell type tucked around these glomeruli which probably affects how the signal is transmitted. These cells are small and densely packed, which gives them the name "granule cells". However, they bear no relation to the granule cells of the cerebellum or cerebral cortex. In fact, they are GABA-ergic, unlike other cells of the same name.

 There are two populations of granule cells in the olfactory bulb – the external, or periglomerular cells, and the internal granule cells. The latter lie deep to the mitral cell layer.

The mitral cell axons travel back to the brain via the olfactory tract. The main target of the olfactory tract is the primary olfactory cortex in the medial temporal lobe. However, the sense of smell is heavily interconnected with all parts of the limbic system.

Does anything about this system strike you as odd? The olfactory system disobeys a general rule of sensory systems – it does not have to pass through thalamus before reaching cortex. However, there is a very good reason why not; olfactory cortex is an old and primitive structure, and in fact has only four cellular layers, unlike the 6-layered cortex we are accustomed to. The rule that sensory information must pass through thalamus to get to cerebral cortex is still true, but only for 6-layered cortex, or neocortex. This description applies to almost every area in the frontal, parietal, occipital, and temporal lobes.

B. The Amygdala

If you remember only one word about the amygdala, the word is FEAR. The amygdala is the nucleus responsible for the lurch you feel in your stomach when you turn around in a dark alley and notice someone following you. It couples a learned sensory stimulus (man in ski mask in alley = danger) to an adaptive response (fight or flight). On the basis of this information, you should be able to guess the primary inputs to and outputs from the amygdala.

Inputs: the amygdala must get sensory input, and it must be fairly highly processed input to recognize the elements of a scene that signal danger. The association areas of visual, auditory, and somatosensory cortices are the main inputs to the amygdala.

Outputs: the amygdala must be able to control the autonomic system, to provoke such an instant sympathetic response. The main outputs of the amygdala are to the hypothalamus and brainstem autonomic centers, including the vagal nuclei and the sympathetic neurons.

The amygdala is also involved with mood and the conscious emotional response to an event, whether positive or negative. To this end, the amygdala is also extensively interconnected with frontal cortex, mediodorsal thalamus, and the medial striatum. 

These two images of the amygdala demonstrate that there are discrete groups of cells within the large nucleus. The deep group, which includes the lateral, basal, and accessory basal nuclei, is responsible for collecting the input from sensory cortex. The more dorsal group, which includes the central and medial nuclei, receives projections from the deep group and sends the signal out to autonomic centers.

It is very difficult to study the amygdala in humans, because selective bilateral damage of the amygdala is so rare. One of the few existing case studies reported a woman with a bilateral degenerative disease who was unable to recognize the expression of fear in human faces. Monkeys with lesioned amygdalas are unable to recognize the emotional significance of objects, and for example, show no fear when presented with a snake or another aggressive monkey. This has disastrous social consequences for the monkey.

Epilepsy surgery provides an opportunity to stimulate areas of the brain to determine the extent of the epileptic focus. In some such patients, the amygdala was electrically stimulated, which caused intense hallucinations, often accompanied by fear.

C. The Hippocampus and Memory

If the amygdala is FEAR, then the hippocampus is MEMORY. To understand exactly how the hippocampus is involved in memory, however, you must first know a little about memory.

There are at least three different types of memory. The most short term is working memory. Working memory is like the RAM of a computer. It is the type of memory that enables you to spit back the last sentence of a coversation when someone accuses you of not listening. Like the RAM of a computer, it is crucial for performing some common operations in your head: adding numbers, composing a sentence, following directions, etc. Also like a computer, the space devoted to that operation is recycled as soon as you turn to something else. It does not become a permanent memory. Working memory does not require the hippocampus; it is probably a cortical phenomenon.

The second type is what we most commonly associate with "memory". This is long-term or declarative memory, and is composed of all the facts, figures, and names you have ever learned. All of your experiences and conscious memory fall into this category. It is analogous to the hard drive of a computer. Although no one knows exactly where this enormous database is stored, it is clear that the hippocampus is necessary to file away new memories as they occur.

The third type is procedural memory, and is probably the most durable form of memory. These are actions, habits, or skills that are learned simply by repetition. Examples include playing tennis, playing an instrument, solving a puzzle, etc. The hippocampus is not involved in procedural memory, but it is likely that the cerebellum plays a role in some instances.

The significance of the hippocampus is driven home by a famous patient named H.M. As part of an epilepsy surgery, doctors removed most of his medial temporal lobes. Since that surgery, in 1953, he has formed no new memories. He can remember his childhood and everything before the surgery, and he still has working memory and the ability to form procedural memories. You can have a normal, lucid conversation with him, but if you leave the room for a moment, when you return he will not remember you or the conversation. He has completely lost the ability to lay down declarative memory.

Therefore, the hippocampus is critical in laying down declarative memory, but is not necessary for working memory, procedural memory, or memory storage. Damage to the hippocampus will only affect the formation of new declarative memories.

The mechanisms of the hippocampus are not entirely understood. The formation of memories probably involves long term potentiation, or LTP. This is a molecular process which strengthens groups of synapses that are repeatedly used. LTP is not sufficient to explain the storage of memory, though.

D. The Anatomy of the Hippocampus

The hippocampus is a scrolled structure located in the medial temporal lobe. In a coronal section, it looks like this:

The hippocampus can be divided into at least five different areas, as labeled above. The dentate gyrus is the dense dark layer of cells at the "tip" of the hippocampus. Areas CA3 and CA1 are more diffuse; the small CA2 is hard to distinguish between them. (CA stands for cornu ammonis, from its ram's horn shape.) The subiculum sits at the base of the hippocampus, and is continuous with entorhinal cortex, which is part of the parahippocampal gyrus. There is essentially a one-way flow of information through the hippocampus, as diagrammed below.

 Information enters the hippocampus by jumping across what appears to be a gap between the subiculum and dentate gyrus. This tract is called the perforant path, as it perforates the space between the two. The entorhinal axons then synapse on cells in the dentate gyrus. The dentate neurons, in turn, send axons to CA3; these are called mossy fibers. ("Mossy fibers" is a morphological description for axons with large bulbous terminals, and these are unrelated to those in the cerebellum.) CA3 sends axons called Schaeffer collaterals to CA1, which sends yet another set of fibers to the subiculum. The subiculum is responsible for the output of the hippocampus: it can either send axons directly to the hypothalamus and mammillary bodies via the fornix (remember the fornix?), or it can pass along the information back to entorhinal cortex, which will relay it all back to sensory cortex. It is essentially one continuous pathway that begins in sensory cortex, traverses the hippocampus (loop-the-loop), and returns to sensory cortex. Somewhere in there, memory is born.

E. Diseases of the Hippocampus

The hippocampus is particularly vulnerable to several disease processes, including ischemia, which is any obstruction of blood flow or oxygen deprivation, Alzheimer's disease, and epilepsy. These diseases selectively attack CA1, which effectively cuts through the hippocampal circuit. Below is a photograph of a normal hippocampus and one which has been deprived of oxygen.

 You should be able to see the degeneration of CA1 (labeled) and the absence of cell bodies (stained purple). A stroke can have this effect, but there must be bilateral damage of the hippocampi to affect memory. Therefore only situations that deplete blood or oxygen flow to the entire brain will produce a memory deficit. The pathology of severe temporal lobe epilepsy looks very similar to ischemic damage.

Alzheimer's disease, although it affects the entire brain, is particularly hard on the CA1 region. Below is a photograph of the hippocampus of an Alzheimer's patient, with the CA1 region magnified. Both extracellular plaques and intracellular tangles are visible – these are the pathological hallmarks of the disease.



Sleep and Language

A. Sleep

During sleep, we are essentially cut off from the sensory world. We do not hear, feel, taste, or smell, and we would not see if our eyes were pulled open. Everyone has different thresholds during sleep, though; enough of any stimulus will wake us. How does the brain manage to cut off sensory input, yet still let in the really important (or insistent) stimuli? The answer lies in the thalamus. Remember, no sensory information gets up to the cerebral cortex without first passing through the thalamus. If the gate of the thalamus is closed, then the cortex can shut out the world and go into sleep-mode.

B. The EEG

Electrophysiologists define sleep in terms of the electrical activity of the brain. Just like the electrical activity of the heart can be measured with electrodes on the chest, depolarizations in the brain can be recorded at the scalp. This technique is the electro-encephalogram, or the EEG. An EEG is an average of all the electrical events going on in the brain, and in an awake person it would look something like this:

There is no apparent pattern to the activity, and the activity doesn't seem to be very strong. This is due to the fact that there are so many unrelated simultaneous events going on that many will cancel each other out, leading to a tracing which looks nearly flat. This type of EEG activity is called desynchronous, and is low amplitude but high frequency.

During sleep, the multitude of electrical events begin to fall into sync with one another, and the tracing takes on a new appearance:

Notice that the fluctuations are larger and slower than in the awake state. This pattern is called synchronous, and is high amplitude but low frequency.

There are four recognized stages of sleep, from the first and "lightest" stage to the deepest fourth stage. At night, you progress from stage 1 to stage 4 in the first hour of sleep, and spend the rest of the night cycling up and down between 1 and 4. The EEG gets progressively more synchronous with each deeper stage. Every time you return to stage 1, you enter REM sleep – a period of sleep characterized by rapid eye movements. REM sleep is also called paradoxical sleep, because the body appears to be more deeply asleep than in any other stage, but the EEG looks very much like the waking brain. The desynchronous activity of the brain may be due to dreaming, which also occurs during REM sleep.

C. The Ascending Reticular Activating System

Early on, someone noticed that if the midbrain of a cat was transected (at point A, below), the cat fell into a coma – their EEG became permanently synchronized. This finding alone is not too surprising. However, if the transection was made down in the medulla (at point B), the cat was only paralyzed, not comatose. The most surprising phenomenon was that if the rostral stump of the transected midbrain was electrically stimulated (blue arrow), the cat "woke up" – according to its EEG.

From these experiments it was concluded that there was some pathway originating in the pons or midbrain that ran forward into the cerebrum and stimulated wakefulness. The pathway was thought to originate with a group of neurons in the brainstem, the reticular formation. Therefore it was named the ascending reticular activating system.

They were close. In fact, the ascending pathway originates from a group of neurons around the fourth ventricle in the rostral pons (near midbrain). Most of these neurons are acetylcholinergic, and project to the thalamus, controlling whether the gate is open or closed. The key is in the action of acetylcholine. Acetylcholine cannot, by itself, activate or shut down the neurons of the thalamus. Instead it sensitizes them. By slightly depolarizing the thalamic neurons (it does this by closing a hyperpolarizing potassium channel), the ascending system can make the thalamus more sensitive to sensory input. This situation would correspond to an awake, alert state. Let's look at the whole system:

The acetylcholinergic neurons project both to the sensory areas of thalamus (such as VPL) and to the reticular nucleus, a layer of cells that wraps around the thalamus like the rind of an orange. This "reticular" has nothing to do with the "reticular" in the brainstem! The fact that the ascending reticular activating system targets the reticular nucleus is only maddening coincidence. The reticular nucleus of the thalamus has a general inhibitory effect on sensory thalamus. Now, although both areas are receiving acetylcholine, they have different receptors and respond in different ways. Sensory thalamus is sensitized by acetylcholine (or "facilitated") as described above, but the reticular nucleus is inhibited by acetylcholine. We can redraw the situation like this:

 So what happens when the brain is awake? The cholinergic cells are active, so they facilitate sensory thalamus and inhibit the reticular nucleus. The inhibition of the reticular nucleus actually excites the sensory thalamus as well (negative x negative = positive). As a result the thalamus lets all sensory information through, and cortex is highly active and desynchronized dealing with all the input.

And when the brain is asleep? Now the ascending system is quiet, so sensory thalamus is not particularly sensitive. In addition, the reticular nucleus is freed from inhibition, so it can inhibit the sensory thalamus. The net effect is that thalamus is very insensitive to sensory stimuli, the gate is closed, and the cortex can rest. An interesting property of the thalamic neurons is that when hyperpolarized, they have slow intrinsic waves of activity, similar to the pacemaker of the heart. This activity may be the source of the slow synchronous pattern of the sleeping EEG. It also may function to keep the cortex in shape, ensuring that even when you are asleep the cortical neurons are active.

A summary:



ACh system active

ACh system inactive

sensory thalamus facilitated

sensory thalamus inhibited

reticular nucleus inhibited

reticular nucleus active

thalamocortical neurons active

thalamocortical neurons in slow rhythm

EEG desynchronous

EEG synchronous


Any student who regularly attends classes will recognize that these two states are merely the endpoints of a single continuum.

D. Dreaming

Dreaming occurs during REM sleep, the "paradoxical" sleep stage. Curiously, the ascending acetylcholinergic system actually turns on – it is as though the brain wakes up internally. Yet for some reason the person remains unconscious and unaware. Dreams generally do not make it to conscious memory unless the dreamer is awakened from the dream itself.

How is it that the cholinergic system can be on and the sleeper still unconscious? The answer probably lies in other neurotransmitters and nuclei of the rostral pons. The dorsal raphe nuclei, a cluster of serotonergic cells, and the locus ceruleus, a group of noradrenergic neurons, also play a role in sleep. They may help to keep consciousness suppressed during dreaming.

One of the striking things about REM sleep is the absolute stillness of the body. During most stages of sleep we toss and turn, but in REM sleep only the eye muscles twitch (and, for some unknown reason, the middle ear muscles!). This is due largely to a system of descending inhibition. Dreaming turns on a group of cells in the medulla that descend down the spinal cord and inhibit motor activity. Very specific lesions of these cells (a rare event) lead to a phenomenon called "violent sleeping", where the dreamer physically acts out his or her dreams. This is different from sleepwalking, which usually does not occur during REM sleep.

E. Language

Language, in most people, appears to be localized almost exclusively to the left cerebral hemisphere. Knowing what you know about the organization of the brain, where would be the most logical place to put a cortical area in charge of the production of language? First and foremost, you need fine control over the tongue and mouth. It would make sense to put your cortical area near the mouth section of motor cortex. Sure enough, just rostral to the motor-mouth area of the precentral gyrus is a small area that controls speech. It is called Broca's area, after the physician who discovered it in 1861. Broca had a patient who, after a stroke, completely lost the ability to speak. The patient could apparently understand language, but the only syllable he could produce was "tan", over and over again. After Tan's death, Broca performed an autopsy and determined the site of the stroke. Broca's area is shown below:

What about language comprehension? Where is the most logical place to put the comprehension area? First you must decide if language is primarily visual or auditory. When you read, do you "hear" the words in your head? When you listen, do you "see" the words as written? Which came first, written or spoken language? You probably agree that language is more of an auditory phenomenon than visual. As expected, the language comprehension area is just adjacent to auditory cortex, where the parietal lobe meets the temporal lobe. This area was discovered by Wernicke in 1874, by a studying patients with select comprehension deficits. These patients could not understand language, spoken or written, and could apparently produce copious flowing speech. Their speech, however, made absolutely no sense. Subjects and verbs would be strung together in a seemingly grammatical order, like fragments of real sentences, but the sentences seemed to bear little relation to what the patient was trying to express. Presumably the patients could not understand what came out of their own mouths. Wernicke's area is shown below:

But language is far too complex to be broken down into two discrete cortical areas. Obviously there are visual and manual components to language, for reading and writing. Where does sign language fit in? How do you explain a patient whose only deficit is an inability to name tools? He can describe the use of a hammer but not its name. How does a collection of syllables – a person's name – trigger the face, personality, birthdate, or voice of that person in your memory? Language is probably located all over the brain, with extensive crosstalk between areas. The discrete areas of Broca and Wernicke may be necessary for language, but they are certainly not sufficient.


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