Lab 5: Motor Systems

Lab Summary

The purpose of this laboratory is to familiarize you with the nuclei and tracts that have a role in the execution and direction of movements. 

SECTION 1: Basal Ganglia

SECTION 2: Cerebellum

SECTION 3: Nuclei & Tracts of Descending Systems

SECTION 4: Review

Basal Ganglia

The purpose of this laboratory is to familiarize you with the nuclei and tracts that have a role in the execution and direction of movements. Major relationships are shown in Figure 5.1.

Although conscious movement is ultimately under the control of the cerebral cortex, the execution of coordinated, purposeful movements also requires the participation of the basal ganglia and cerebellum. The collaborative systems involved in movement are frequently grouped into the ‘pyramidal system’ denoting the descending corticospinal pathways that travel through the pyramids at medullary levels and the ‘extrapyramidal system‘ that includes the basal ganglia, cerebellar circuits and connections that play an important role in modifying and maintaining coordinated conscious and unconscious movements. The basal ganglia and cerebellar circuits receive direct input from the cerebral cortex as well as from ascending sensory pathways and provide a mechanism for sensory modification of ongoing movements, as well as the circuitry needed for motor sequence and habit formation.

You will be able to see these structures in a variety of materials available in the laboratory; some of these will be handed out by instructors. These include: 1) sliced brains in the frontal and horizontal planes from the first lab session; 2) large black and white slides of brains sectioned in the horizontal and coronal planes; 3) the Kodachromes on the light boxes in TAC room 232; 4) fiber-stained and cell-stained sections through the basal ganglia and cerebellum; 5) the fiber-stained brainstem sections in your slide collection; and 6) the fiber-stained and cell-stained series of coronal cuts through the monkey brain in the slide collection. Explore as many of these as possible. Experience with the appearances of the structures using different stains and different planes of section is important. In this first section, we look at the basal ganglia and related structures. 

Basal Ganglia and Related Structures

The basal ganglia is a term for a collection of interconnected nuclei embedded within the cerebral hemispheres and midbrain. The major nuclei of the basal ganglia include: the caudate and putamen which together constitute the striatum or neostriatum; the internal (GPi) and external (GPe) segments of the globus pallidus, that together with the putamen are considered the lentiform nuclei; the substantia nigra pars compacta (SNc) and pars reticulata (SNr); and the subthalamic nucleus (ST).

The primary source of inputs to the basal ganglia extrapyramidal system is the cerebral cortex. All cortical areas project to the caudate-putamen complex in a topographically organized manner. The gradient of corticostriatal projections is that rostral cortical regions project most heavily to the rostral striatum with caudal cortical regions projecting to the caudal striatum. The principal output of the basal ganglia circuits is through the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr) to the ventral anterior (VA) and mediodorsal (MD) thalamic nuclei. These thalamic nuclei then project to cortical areas, including the regions that give rise to descending corticostriatal projections. In summary:

Cortex → Caudate Putamen → Globus Pallidus → VA, VL → Cortex

Interposed between the input areas of the striatum and the output areas of the GPi and SNr is an important circuitry involving the external segment of the globus pallidus (GPe), the subthalamic nucleus and the substantia nigra pars compacta (SNc).

Begin to get an appreciation of the distribution and spatial organization of the different components of the basal ganglia by examining the Horizontal Basal Ganglia & Thalamus and Coronal Basal Ganglia & Thalamus sections in Figure 5.2-5.3.

These are from a widely spaced series of horizontal and coronal sections through human brains stained with a fiber stain. When studying these sections, try to identify their superior to inferior, and anterior to posterior positions using the horizontally sliced fixed brains from the first lab. Indicate the position of each slide on the sagittal brain illustration in Interactive 5.1.

It is very important to actually locate the plane of section of each slide on the preserved brains in each lab. This repeated experience will pay off by building a three-dimensional understanding of the brain.

When examining the stained series of horizontal and coronal sections, first look at each section in the unlabeled view and try to locate the head, body and tail of the caudate, the putamen, the globus pallidus external and internal segments, the subthalamic nucleus and the substantia nigra. Think about affiliated structures like the internal capsule, thalamus, zona incerta and cerebral peduncle. Not every structure will be in each section. Think about what structure you would expect to find when you look at each section. 

Identify and locate the boundaries and neighboring structures of the:

Caudate nucleus – the caudate nucleus is a “C” shaped structure forming the lateral wall of the lateral ventricle. The large “head” of the caudate sits in the frontal lobe lateral to the anterior horn of the lateral ventricle. The “body” of the caudate follows the ventricle posteriorly as it runs over the thalamus and then transitions to the ‘tail’ of the caudate sitting in the lateral portion of the inferior horn of the ventricle (Figure 5.4).

Putamen – is found lateral and ventral to the head and body of the caudate nucleus, and is separated from the caudate by the fibers of the internal capsule. The putamen is marked by fascicles of myelinated axons directed toward the globus pallidus, the major efferent target of the putamen.

Globus pallidus – contains a homogeneous distribution of myelinated fibers that gives the nucleus its characteristic pale appearance.

The internal or medial segment of the globus pallidus (GPi) is the principal output structure of the motor circuit of the basal ganglia and is found ventral-medial to the putamen. Output from GPi is directed to the thalamus,  via two routes (Figure 5.5):  l) the ansa lenticularis, a collection of GPi axons that pass medially to loop around the internal capsule and then turn dorsally towards the thalamus  and 2) the lenticular fasciculus,  GPi axons that pass through the internal capsule, looping around the zona incerta (a part of the thalamic reticular nucleus) on the way to the thalamus. . Before reaching the thalamus, these 2 pathways merge to become the thalamic fasciculus which provides innervation mostly to theVA thalamic nucleus and, to a lesser extent, to the ventral lateral (VL) and centromedian (CM) thalamic nuclei . The ansa lenticularis, lenticular fasciculus and thalamic fasciculus ( Figure 5.6 )constitute the H fields of Forel.

The external or lateral division of the globus pallidus (GPe) is involved in the indirect pathway of the basal ganglia circuitry. Its principal input is inhibitory from the enkephalin and GABAergic neurons of the caudate and putamen. Its primary output is inhibitory to the subthalamic nucleus using GABA. Loss of striatal inhibition of the GPe through the indirect pathway, as is seen in the early stages of Huntington’s disease, is thought to increase the GPe inhibition of the subthalamic nucleus, leading to less excitation of the inhibitory pallido-thalamic neurons of the GPi. The net effect is less inhibition of the motor thalamus and hyperkinetic movements.

Substantia nigra – extends for the length of the mesencephalon, sits posterior (dorsal) and medial to the cerebral peduncles, anterior (ventral) and lateral to the Red nucleus and is subdivided into two zones.

The pars compacta (SNc) region sits dorsal and medial to the pars reticulata and appears black in fresh or fixed tissue slices due to its closely packed cells containing melanin granules. The cells of the pars compacta synthesize dopamine and project to the corpus striatum. The degeneration of these cells in Parkinson’s disease and the loss of their dopamine projection to the striatum is the primary mechanism responsible for the motor symptomology of this hypokinetic movement disorder.

The pars reticulata (SNr) sits ventral and lateral in the midbrain, lies adjacent to the cerebral peduncle, is more loosely organized than the compacta region, and is the non-pigmented region of the SN containing primarily GABAergic neurons. It derives its name from the reticulated appearance due to the presence of scattered fascicles of corticonigral, pallidonigral and nigrostriatal fibers that course through this region. The SNr is the primary output for the basal ganglia motor circuitry for the head and neck. It is also the principal output structure for the cognitive circuit of the basal ganglia innervating the VA and MD nuclei of the thalamus.

Subthalamic nucleus (Figure 5.6) – located just rostral and posterior to the substantia nigra and medial and posterior to the internal capsule. This nucleus is part of the indirect pathway of the basal ganglia circuitry, receives primarily inhibitory input from the GPe and provides excitatory innervation to the GPi.. Damage to the subthalamic nucleus results in diminished excitation of the GPi neurons that in turn diminish inhibition of the thalamus, resulting in excessive thalamocortical excitation that produces hyperkinetic movement of the contralateral extremities called hemiballismus. VA, VL, MD and CM thalamic nuclei (Figure 5.6) – Briefly, the ventroanterior (VA), and ventrolateral (VL) thalamic nuclei are the primary targets of the basal ganglia and cerebellum, respectively. VA receives substantial input from the SNr and GPi of the basal ganglia and limited input from the deep cerebellar nuclei. It then projects to areas of the frontal, prefrontal, premotor and supplementary motor cortices. VL receives its principal input from the deep cerebellar nuclei and a more limited input from the SNr and GPi of the basal ganglia. The cortical targets of VL are the primary and supplementary motor cortices. Although both VA and VL receive some input from both the basal ganglia and cerebellum, VA is considered the primary thalamic nucleus for basal ganglia input to the cortex and VL is the primary relay for cerebellar input. Input to the mediodorsal (MD) nucleus from the basal ganglia is primarily from the SNr and is related to the cognitive circuits of the basal ganglia. The MD then projects to the prefrontal and frontal cortices. The centromedian (CM) nucleus is an intralaminar nucleus of the thalamus and is part of the ascending reticular activating system (ARAS). It receives input from GPi of the basal ganglia and the deep cerebellar nuclei and has widespread projections to the cerebral cortex and striatum. Together, the VA, VL, MD and CM nuclei are the primary thalamic targets of the basal ganglia and cerebellar circuitry and are important in the regulation of movement, thought and the formation of habits.

Be sure to identify each of the structures discussed above in the Horizontal Basal Ganglia & Thalamus sections (Figure 5.2) and the Coronal Basal Ganglia & Thalamus sections (Figure 5.3). Note the transitions of the structures of the corpus striatum in the rostral-caudal and dorsal-ventral directions and their relationship to the thalamus and internal capsule. Most rostral, the putamen and caudate are joined. The first coronal section is just posterior to this junction, but you can find the junction on the coronal sections through the monkey brain in your slide collection. Using the horizontal and coronal sections you should be able to locate and identify the caudate, putamen, globus pallidus, anterior commissure, internal capsule, external capsule, and thalamus in these sections. The zona incerta, subthalamic nucleus and joining of the ansa lenticularis, lenticular fasciculus and thalamic fasciculus (a region known as the fields of Forel) are best seen in brainstem sections through the midbrain (Figure 5.6). Review the Kodachromes in room 232. These show more closely spaced sections and will reveal the gradual changes in each direction. Particularly, study the sagittal sections to see the relationship of the corpus striatum to the internal capsule, and of the subthalamic nucleus to the substantia nigra.

Examine the blood supply of the thalamus and basal ganglia (Figure 5.7). Note that the medial striate artery (blue in Fig 5.7) a branch of the anterior cerebral artery, supplies the most rostral regions of the caudate, putamen and internal capsule. The rest of the caudate, putamen, and internal capsule, and the lateral part of the globus pallidus are supplied by the lenticulostriate branches of the middle cerebral artery (yellow in Figure 5.7). The anterior choroidal artery (green in Figure 5.7) that arises from the internal carotid supplies medial areas, including the globus pallidus. The full arterial supply of this region can be appreciated in coronal and axial sections taken from Blumenfeld (2002).

Review the lecture on the basal ganglia and trace the direct and indirect pathways of information flow through the basal ganglia for motor and cognitive domains, as well as the impact of dopamine on these circuits (Figure 5.8).

Be aware that in addition to the motor (body movement) and cognitive (prefrontal) loops in the basal ganglia, there are similar circuits for oculomotor movements and emotional expression (limbic). You should be aware of the component structures that make up each of the functional loops for body movement, oculomotor movements, cognition and emotion (Figure 5.9).

Cerebellum

The cerebellar cortex receives major inputs from: 1) the cerebral cortex via relays in the pontine nuclei, pontocerebellar fibers and the inferior olive; 2) the red nucleus via the inferior olive; 3) the vestibular nuclei; 4) the spinal cord  directly, and indirectly via the inferior olive; and 5) noradrenergic (locus coeruleus) and serotinergic (raphe nuc.) fibers from brainstem nuclei. The inputs are all via mossy fiber endings, except for those from the inferior olive which terminate as climbing fibers on individual Purkinje neurons. The major efferents of the cerebellum arise from the 4 pairs of deep cerebellar nuclei and project to the 1) cerebral cortex (especially the precentral gyrus) via the VA-VL complex of the thalamus, 2) red nucleus, 3) vestibular nuclei and oculomotor nuclei via the MLF, 4) reticular formation in the pons and medulla, and 5) spinal cord.

Gross Orientation of the Cerebellum

Use the whole and sagittal fixed brain specimens to identify the primary cerebellar subdivisions. The cerebellum can be divided into a central region that is the vermis and the expansive lateral hemispheres. A further division of these regions into anterior, posterior and flocculonodular lobes is based upon the position of the primary and posterolateral fissures. Locate the primary fissure and the posterolateral fissure on the medial surface of the cerebellum in the fixed brains (Figure 5.10). These fissures are important because they form the boundaries of the three major functional areas of the cerebellum: the anterior lobe (paleocerebellum), the posterior lobe (neocerebellum) and the flocculonodular lobe (archicerebellum). Follow these fissures out onto the intact surface of the cerebellum. In humans the hemispheres have expanded so greatly that they have partly grown over the vermis. While looking at the cut edge of the cerebellum you can also see that the cerebellar cortex is divided into folia (somewhat comparable to gyri in the cerebrum) by the many infoldings of the hemispheres. Bundles of white matter passing to and from the cortex form the core of each folium.

The flocculonodular lobe (archicerebellum) and fastigial nucleus of the cerebellum receive afferents from the ipsilateral vestibular nuclei and are considered the vestibulocerebellum. The output of this region is to the ipsilateral vestibular and reticular nuclei and is an important influence on posture, balance and equilibrium. The anterior lobe (paleocerebellum) receives input from the spinocerebellar tracts and is concerned with the regulation of muscle tone. The posterior lobe (neocerebellum) receives input from the contralateral cerebral cortex via the pontine nuclei and is most concerned with somatic motor function (Figure 5.11).

There is also a functional medial to lateral organization for the vermis and hemispheres. Similar to the flocculonodular lobe, the vermis receives input form the vestibular nuclei and then acts to regulate proximal limb and trunk coordination through outputs to the vestibular and fastigial nuclei. Action at the level of spinal cord motor neurons is then relayed by the vestibulospinal, fastigiospinal and reticulospinal tracts. The intermediate part of the cerebellar hemisphere (the vermis is medial) is involved in the control of distal limb coordination through its outputs via the globose and emboliform nuclei. Finally, the large lateral areas of the hemispheres participate in motor planning for the extremities with the principal output occurring via the dentate nucleus.

Cerebellar Connections

The cerebellum is connected with the rest of the brain by way of 3 fiber stalks: the superior, middle, and inferior cerebellar peduncles (also known as the brachium conjunctivum, brachium pontis, andrestiform body, respectively).

 Use the whole brains, brain stem preparations, and sagittal half brains to locate the three cerebellar peduncles. In addition to identifying these on the fixed tissue specimens, be sure that you can identify each of these on the brain stem sections. . Revisit the medullary and pontine sections from Lab 4 to locate the three cerebellar peduncles. As you do this, think about the origins and sites of termination of the axons that make up these structures in the brain stem and spinal cord.

Superior cerebellar peduncle – contains mainly efferent fibers. Running in the superior cerebellar peduncle are axons projecting from the deep cerebellar nuclei (dentate, emboliform, and globose) to nuclei in the brain stem and thalamus. Specific targets of these axons are the contralateral red nucleus and the contralateral VA-VL complex of the thalamus (which then projects to motor cortex). Locate the decussation of the axons of the superior cerebellar peduncle in sections at the level of the inferior colliculus in the caudal midbrain. A small number of afferent axons enter through this peduncle coming from the ventral spinocerebellar tract, in addition to fibers arising from the locus coeruleus and raphe nuclei of the brainstem related to the widely projecting modulatory activating systems of the brain. Since the majority of cerebellar efferents cross to the opposite side of the brain on exiting the cerebellum, how does the primary action of the cerebellum come to be on the ipsilateral body?

Middle cerebellar peduncle – appears to be entirely afferent. It contains mainly incoming axons from neurons located in contralateral pontine nuclei in the basal pons. Neurons of the pontine nuclei are the targets of descending inputs related to motor function from areas of the ipsilateral cerebral cortex and then relay this information to the contralateral cerebellar cortex.

Inferior cerebellar peduncle – contains mainly afferent, uncrossedfibers. arising from the dorsal and cuneo- spinocerebellar tracts, ipsilateral vestibulocerebellar projections and also crossed projections from the inferior olive of the medulla. These inputs project to the cerebellar hemispheres.

Cerebellar Histology

The deep cerebellar nuclei are, from medial to lateral the: Fastigial, Globose, Emboliform and Dentate (Figure 5.12) . Identify the nuclei in your myelin-stained sections of the human brain.

Cerebellar output pathways are:

On microscope slides you can identify the cerebellar cortical layers and various neural elements in appropriately stained tissue sections.

Start by examining a Kluver-Barrera (cell and myelin stain) stained slide of monkey cerebellum that will be given to you by your instructor. Look first at the slide using the low power of your microscope or a projector. In these sections you can locate the fastigial and dentate nuclei. Now look at the cortex. Identify the areas containing axons passing to and from the cerebellar cortex (central white matter and folial white matter). Then identify the 3 layers of the cerebellar cortex. From the outside-in they are: the molecular layer, the Purkinje cell layer, and the granule cell layer. With your microscope you may be able to identify some of the 5 neuron classes of the cerebellar cortex (Figure 5.13A): 1) Stellate cells (outer molecular layer), 2) basket cells (inner molecular layer), 3) Purkinje cells (Figure 5.13B) (Purkinje cell layer also known as ganglionic layer), 4) Golgi II cells (usually in upper part of the granule cell layer), and 5) granule cells. Besides the visible neuronal cell bodies, what types of fibers are present in each layer? Bear in mind that only one of the cell types present in the cerebellar cortex, the granule cell, is known to have a net excitatory effect on the neurons it contacts.

Review the circuitry of the cerebellum thinking about the functional role of the different cellular groups to the inputs and outputs (Figure 5.14)

Nuclei and Tracts of Descending Systems

Cortical Areas Giving Origin to Corticospinal and Corticonuclear Pathways

Fibers of the corticospinal or pyramidal tract originate from pyramidal cells in lamina V of the cerebral cortex. Of the fibers composing the corticospinal tract (CST):

25% arise from motor cortex, area 4 of Brodmann. Approximately 3-5% of these fibers arise from giant pyramidal cells (Betz cells; Figure 5.16) of cortical layer V and the remaining axons arise from typical pyramidal neurons of layer V. 

Other cortical areas providing input to the CST include sensory cortex, areas 3, 1, and 2 which contribute approx. 30% of all fibers, the premotor cortex, area 6, contributing approx. 30% of fibers, and the superior (posterior) parietal lobule, areas 5 and 7 contributing approx. 15%. 

Primary motor cortex (Brodmann’s Area 4). On the whole brain, locate the central sulcus. The primary motor cortex lies within the rostral bank and on the surface of the precentral gyrus. Recall the topographical organization of this region, particularly locating the areas that control the legs and feet, the hands, and the face (Figure 5.17). Axons of the corticospinal and corticonuclear tracts arise from pyramidal projection neurons in layer 5. Within the primary motor cortex (area 4), a subset of the corticospinal neurons are characterized by the large size of the soma andare called Betz cells (Figure 5.16) 

Somatosensory cortex (Brodmann’s Areas 3,1 & 2). Somatosensory areas (Areas 3, 1 & 2) lie immediately posterior to the central sulcus and contribute approximately 30% of the fibers that make up the corticospinal and corticonuclear tracts.

Premotor cortex (Brodmann’s area 6). Lies immediately rostral to the primary motor cortex and also contributes approx. 30% of the fibers to these descending tracts.

Voluntary Movement

Figure 5.18, identifies critical areas for the initiation and execution of voluntary movements. Posterior parietal areas 5 and 7 serve important roles in the identification and localization of the target. Premotor area 6 helps provide a plan of action. Finally, primary motor cortex provides descending input to brainstem and spinal motor neurons to execute the movement.

Tracts and Nuclei

Internal capsule. On the Horizontal Basal Ganglia & Thalamus sections, and on the horizontally sliced fixed brain sections, locate the anterior limb, posterior limb and the genu of the internal capsule. With the help of your instructors and Figure 5.19 and Figure 5.20), study the locations of the descending corticospinal, corticonuclear (sometimes referred to as corticobulbar) and corticopontine tracts.

Horizontal view of the internal capsule. Top is anterior, left is medial, bottom is posterior and right is lateral.

What is the function and target of these 3 classes of fibers? The topographical organization of axons running in the corticospinal tract is maintained, such that axons for the cervical levels of the cord are medial and rostral to those for lumbar and caudal levels of the cord. Trace the continuation of the internal capsule into the cerebral peduncles and then into the pons on your serially cut fresh brains and in the Horizontal Basal Ganglia & Thalamus and Coronal Basal Ganglia & Thalamus sections (Figures 5.2-5.3). Be sure to also review the transition of the internal capsule into the cerebral peduncles, pons and the medulla using the Kodachromes on the light boxes in the demonstration room (TAC N232).

Figure 5.20 Horizontal MRI sections revealing the positions of corticospinal and corticonuclear fibers for the face (F), arms (A), trunk (T) and legs (L) in the internal capsule (top) and cerebral peduncle (bottom). Remember the somatotopy rule: upper body is always medial to lower body except in the cortex, posterior columns and medial lemniscus. 

Cerebral peduncles. Analyze the organization of the descending tracts that make up the cerebral peduncles. The corticospinal fibers are arranged with the axons bound for cervical levels of the spinal cord found anterior and medial and the lumbar-bound fibers posterior and lateral (Figures 5.20 & 5.21).

Coronal section of the Midbrain. Note the positions of corticospinal, corticonuclear (corticobulbar) and corticopontine fibers from the different cortical lobes.

Corticospinal tract. Retrace this tract through the pyramids, to the decussation in the caudal medulla and into the spinal cord using the medullary and pontine sections from Lab 4. Examine virtual microscope Interactive 2.5 to identify the position of the descending corticospinal axons. Can corticonuclear axons be found at this level? Where, or why not? The cervical sections of the spinal cord on this slide were taken from above and below the level of the spinal cord transection. Note the areas of axonal and myelin degeneration in the section inferior to the transection . The regions normally occupied by the descending tracts are visible due to degeneration of the constituent axons resulting from their separation from the neuron body at higher levels of the cord. Why does separation from the soma result in axonal degeneration in these areas? Also note that a small percentage of fibers do not cross and  form the anterior (ventral) corticospinal tract.

Red nucleus (Figure 5.21 & 5.22A). This large  nucleus is readily found in the midbrain, dorsal to the substantia nigra. The rubrospinal tract crosses immediately after the fibers leave the nucleus and assume a dorsolateral position in the brainstem and throughout the spinal cord. The decussating fibers can often be seen immediately below the oculomotor nuclei.

Superior colliculus (Figure 5.21 & 5.22B). Deep layers of this nucleus give rise to the tectospinal tract. The axons pass ventrally below the periaqueductal gray and cross, taking a midline position throughout the brainstem and spinal cord. In the lower brainstem, the tectospinal tract is ventral to the MLF and dorsal to the medial lemniscus. In the spinal cord these axons travel with the MLF in the anterior medial white matter and terminate in the anterior horn at cervical levels. They play an important role in the coordination of head and eye movements.

Lateral vestibular nucleus. Uncrossed axons descend from this nucleus to all levels of the spinal cord as the lateral vestibulospinal tract. It projects to all levels of the spinal cord, terminating in the medial portions of the anterior horn to innervate interneurons and motor neurons controlling the proximal, axial and girdle musculature. It plays a role in maintaining balance and equilibrium.

Medial vestibular nucleus. Uncrossed axons descend with the MLF to cervical levels of the cord, terminating in the medial portions of the anterior horn to innervate interneurons and motor neurons controlling the positioning of the head and neck.

Nuclei reticularis pontis caudalis and oralis (rostral and caudal nuclei of the pontine reticular formation). Reticular formation cells in the tegmentum of the pons above the medial lemniscus send uncrossed axons to all levels of the cord, forming the pontine reticulospinal tract. Axons terminate on interneurons of the anterior horn for the unconscious control of posture and gait related movements.

Nucleus reticularis gigantocellularis. Reticular formation cells in the tegmentum of the medulla above the medial lemniscus send uncrossed axons to all levels of the cord. Axons terminate on interneurons of the anterior horn for the unconscious control of posture and gait related movements.

Review the areas of the spinal cord white matter and ventral horn that receive each of these projections (Figure 5.22A), and the predominant effect of each (facilitatory or inhibitory to flexors or extensors, (Figure 5.22B).

Review