The rest of this chapter examines the regional anatomy of the connections and cellular organization of the cerebellum. Sections through key levels, from caudal to rostral, are used to illustrate the locations of spinocerebellar tracts, the histology of the cerebellar cortex, the deep nuclei, and the efferent projections to the brain stem and thalamus.
Spinal Cord and Medullary Sections Reveal Nuclei and Paths Transmitting Somatic Sensory Information to the Cerebellum
Clarke's nucleus and the accessory cuneate nucleus are the principal nuclei that relay somatic sensory information to the spinocerebellum. Clarke's nucleus is found in the medial portion of the intermediate zone of the spinal cord gray matter (lamina VII) (Figure 13–11). This nucleus forms a column with a limited rostrocaudal distribution (Figure 13–6). In the human, Clarke's nucleus spans the eighth cervical segment (C8) to approximately the second lumbar segment (L2) and relays somatic sensory information from the lower limb and lower trunk. Because the caudal boundary of the nucleus is rostral to the lumbosacral enlargement, afferent fibers from most of the lower extremity first enter and ascend in the gracile fascicle (Figure 13–6). Then they leave the white matter to terminate in Clarke's nucleus. The dorsal spinocerebellar tract originates from Clarke's nucleus. The tract ascends in the outermost portion of the ipsilateral lateral column (Figure 13–11C) and enters the cerebellum via the inferior cerebellar peduncle (Figure 13–11A, B). The other pathway from the lower limb, the ventral spinocerebellar tract, is lateral to the ascending fibers of the anterolateral system (Figure 13–11C). The ventral spinocerebellar tract originates from diverse neurons in the ventral horn. The ventral spinocerebellar tract is a crossed spinal pathway, entering the cerebellum via the superior cerebellar peduncle, where some of the axons re-cross (Figure 13–12).
Brain stem (A, B) and spinal cord (C) nuclei transmitting somatic sensory information to the cerebellum. A. Key pathways for information from the dorsal spinocerebellar and cuneocerebellar tracts. B. Myelin-stained transverse section through the medulla, at the level of the accessory cuneate nucleus and inferior olivary nucleus. The arrow in A indicates the plane of section in B. Myelin-stained section through the upper lumbar cord (C). Note, the anterolateral system axons are located immediately medial to those of the ventral spinocerebellar tract.
Myelin-stained transverse section through the caudal pons and deep cerebellar nuclei. The inset shows the plane of section.
The caudal medulla contains the accessory cuneate nucleus (Figure 13–11A, B), which is rostral to the cuneate nucleus, important for perception (see Chapter 4). (The accessory cuneate nucleus is also termed the external cuneate nucleus.) The accessory cuneate nucleus relays somatic sensory information from the upper trunk and upper limb to the cerebellum, not for perception but for controlling movements. To reach the accessory cuneate nucleus, afferent fibers from the upper trunk, arm, and back of the head first course rostrally within the cervical spinal cord in the cuneate fascicle of the dorsal column (Figure 13–11A). The entire course of the cuneocerebellar tract is within the inferior cerebellar peduncle.
The Inferior Olivary Nucleus Is the Only Source of Climbing Fibers
The inferior olivary nucleus (Figure 13–11B), from which all climbing fibers originate, is a collection of three subnuclei (see Figure AII–8) that have somewhat different connections. It forms an elevation on the ventral surface of the medulla termed the olive (Figure AI–6). The inferior olivary nucleus consists of a convoluted sheet of neurons surrounded by the axons of the central tegmental tract, which originated from the ipsilateral parvocellular division of the red nucleus (see below). Neurons in the inferior olivary nucleus are electrically coupled, resulting in a synchrony of action among local groups of olivary neurons. The principal division of the nucleus (Figure 13–11B) is the largest in humans. Interestingly, in animals this division is associated with the cerebrocerebellum.
Dorsal to the inferior olivary nucleus is the lateral reticular nucleus (Figure 13–11B), which gives rise to a mossy fiber projection to the cerebellum. The lateral reticular nucleus receives sensory information from mechanoreceptors of the limbs and trunk as well as information from the motor cortex, by branches of corticospinal tract axons. Like neurons of the ventral spinocerebellar tract, the lateral reticular nucleus is thought to participate in correcting for movement errors.
The Vestibulocerebellum Receives Input From Primary and Secondary Vestibular Neurons
Purkinje neurons of the flocculonodular lobe send their axons primarily to the vestibular nuclei (Figure 13–11A, B), rather than to the deep cerebellar nuclei, as do Purkinje neurons in other regions of the cerebellum. (Exceptions exist; some Purkinje neurons of the flocculonodular lobe synapse in the fastigial nucleus, and some within the anterior and posterior lobe vermis synapse in the vestibular nuclei.) The vestibular nuclei are the anatomical equivalent of the deep cerebellar nuclei of the vestibulocerebellum because they share two similarities in the sources of afferent input, both: receive a projection from the inferior olivary nucleus and are monosynaptically inhibited by Purkinje neurons.
The flocculonodular lobe projects to the medial, inferior, and superior vestibular nuclei. These nuclei—especially the medial vestibular nucleus—give rise to the medial vestibulospinal tract, for coordinating head and eye movements (Chapter 12). The fastigial nucleus projects primarily to the lateral vestibular nucleus, which gives rise to the lateral vestibulospinal tract, for controlling axial muscles to maintain balance and posture. The vestibular nuclei also contribute to the medial longitudinal fasciculus (Figures 13–11A, 13–12, and 13–15B), which plays a key role in eye muscle control through projections to the extraocular motor nuclei (see Chapter 12). Thus, the vestibulocerebellum has direct control of head and eye position via its influence on the vestibular nuclei.
The Pontine Nuclei Provide the Major Input to the Cerebrocerebellum
The pontine nuclei (Figure 13–12; also Figures 13–8 and 13–15B3, 4) relay information from the cerebral cortex to the cerebrocerebellum. Virtually the entire cerebral cortex projects to the pontine nuclei (see below). Corticopontine neurons originate in layer V of the cerebral cortex, the same layer that gives rise to the corticospinal and corticobulbar neurons. The descending axons course within the internal capsule and basis pedunculi to synapse in the ipsilateral pontine nuclei. The axons of neurons of the pontine nuclei decussate in the pons and enter the cerebellum via the middle cerebellar peduncle (Figure 13–12).
The Intrinsic Circuitry of the Cerebellar Cortex Is the Same for the Different Functional Divisions
The cellular constituents and synaptic connections of the cerebellar cortex are among the best understood of the central nervous system (see Box 13–1). The cerebellar cortex consists of three cell layers, progressing from its external surface inward (Figure 13–13): the molecular layer, the Purkinje layer, and the granular layer, which is adjacent to the white matter. The cerebellar cortex contains five types of neurons, and they each have a different laminar distribution and are excitatory or inhibitory (Figure 13–13B; Table 13–1): (1) Purkinje neuron, (2) granule neuron, (3) basket neuron, (4) stellate neuron, and (5) Golgi neuron. The Purkinje neuron is the projection neuron of the cerebellar cortex; it is located in the Purkinje layer. All others are interneurons.
Nissl-stained section (low-magnification) through the cerebellar cortex (A); schematic drawing of a cerebellar folium (B). High-magnification view of the cerebellar cortex (C).
Table 13–1Neurons and circuits of the cerebellar cortex ||Download (.pdf) Table 13–1 Neurons and circuits of the cerebellar cortex
|Neuron type ||Laminar distribution ||Synaptic action ||Input ||Postsynaptic target |
|Projection neuron |
|Purkinje ||Purkinje ||Inhibitory || |
Mossy fibers→granule neuron-parallel fibers
Deep nuclei; vestibular nuclei
Deep nuclei; vestibular nuclei
Purkinje, stellate, basket, and Golgi neurons
Climbing fiber (+)→Purkinje neuron (−)→Deep cerebellar nuclei or vestibular nuclei
Mossy fiber (+)→Granule neuron (+)→ Purkinje neuron (−)→Deep cerebellar nuclei or vestibular nuclei
Granule neuron (+)→Basket cell (−)→Purkinje neuron
Granule neuron (+)→Stellate cell (−)→Purkinje neuron
Granule neuron (+)→Golgi cell (−)→Granule neuron
Box 13–1 Inhibitory Circuitry of the Cerebellum
The Purkinje neuron is an inhibitory projection neuron: When it discharges, it hyperpolarizes the neurons in the deep cerebellar nuclei or vestibular nuclei with which it synapses. How then can neurons in the deep cerebellar nuclei and vestibular nuclei transmit control signals to the motor pathways when they are only inhibited by Purkinje neuron? The climbing fibers as well as many mossy fibers (from the spinal cord and reticular formation) make direct excitatory synaptic connection onto neurons in the deep nuclei (Figure 13–14A). (Anatomical data suggest that most mossy fibers from the pontine nuclei bypass the deep nuclei, synapsing only in the cortex.) It is thought that these direct inputs to the deep nuclear neurons increase their excitability and help to maintain their background neuronal activity at a high level. Also, intrinsic cell membrane properties, such as high resting inward ionic currents, help to maintain high levels of activity in these neurons. This continuously high level of neural activity is then reduced, or "sculpted," by the inhibitory actions of the Purkinje neurons. Similarly, for the vestibular nuclei, direct excitatory inputs from vestibular afferents and membrane properties help to maintain a high background level of activity.
The activity of Purkinje neurons is inhibited by two groups of interneurons (Figures 13–13B and 13–14A): stellate neurons, located in the outer portion of the molecular layer, and basket neurons, located close to the border between the molecular and Purkinje layers. Because its synapse is located on the cell body, the basket neuron is very effective in inhibiting the Purkinje neuron. These neurons receive their predominant input from parallel fibers. The action of these inhibitory interneurons "disinhibits" Purkinje neurons; they will exert less inhibition on neurons in the deep nuclei and vestibular nuclei.
The third cerebellar cortical inhibitory interneuron is the Golgi neuron, which inhibits the granule neuron. This inhibitory synapse is made in the granular layer, in a complex structure termed the cerebellar glomerulus (Figure 13–13C; clear zones seen under high magnification). Synaptic glomeruli ensure specificity of connections because this entire synaptic complex is contained within a glial capsule. An inventory of the synaptic action of the interneurons of the cerebellar cortex demonstrates that all but the granule neuron are inhibitory (Table 13–1).
The circuitry of the cerebellar cortex. Inset shows a stained Purkinje neuron (Golgi stain). There are two major excitatory inputs to the cerebellum: climbing fibers and mossy fibers. Whereas the climbing fibers synapse directly on Purkinje neurons, the mossy fibers first synapse on granule neurons, which in turn give rise to the parallel fibers, which synapse on Purkinje neurons.
The same two basic circuits are present throughout the cortex of the spinocerebellum, cerebrocerebellum, and vestibulocerebellum; one receiving excitatory input from the climbing and the other, from the mossy fibers. Climbing fibers originate entirely from the inferior olivary nuclear complex (Figure 13–11B) and synapse on Purkinje neurons (Figure 13–14). Climbing fibers make multiple synapses with one Purkinje neuron. Remarkably, each Purkinje neuron receives input from only a single climbing fiber. Individual climbing fibers branch to make contact with no more than about 10 Purkinje neurons.
The other circuit begins with the mossy fibers; the Purkinje neuron is also the target, but not directly (Figure 13–14). Mossy fibers first synapse on granule neurons—the only excitatory interneurons in the cerebellum. Located in the granular layer (Figure 13–13), granule neurons have an axon that ascends through the Purkinje layer into the molecular layer. Here the axon bifurcates to form the parallel fibers, which synapse on Purkinje neurons (Figure 13–14) and other cerebellar interneurons (Table 13–1). Note that the micrograph of the Purkinje neuron (Figure 13–14) is in the plane of the dendritic tree; the right side of the drawing is at right angles to the dendritic tree. Owing to the planar dendritic tree of Purkinje neurons, one parallel fiber will synapse only a few times with a Purkinje neuron, as the axon passes through its dendrites. That axon may synapse on hundreds of Purkinje neurons that are stacked along the folium. Each Purkinje neuron receives synapses from thousands of parallel fibers. The efficacy of parallel fiber input onto a given Purkinje neuron is increased immediately after Purkinje neuron activation by a climbing fiber. Purkinje neurons of the spinocerebellum and cerebrocerebellum project their axons through the cerebellar white matter to synapse on neurons in the deep cerebellar nuclei (Figure 13–12). To reach the vestibular nuclei, Purkinje neuron axons of the vestibulocerebellum travel through the inferior cerebellar peduncle.
The cerebellum is thought to have a modular functional organization organized, in part, by the projections of climbing fibers. Within the different sagittal functional zones (eg, Figure 13–5), there are microzones in which small clusters of Purkinje neurons receive climbing fiber inputs that have similar physiological characteristics, such as processing somatic sensory information from the same body part. The Purkinje neurons in the microzone, in turn, project to a group of neurons in a deep nucleus or vestibular nucleus that receive similar inputs from the olive. Within each functional division there are many microzones. It is thought that each microzone subserves a different aspect of the overall functions of the broader zone, such as regulating the coordination and strength of contraction of different hand muscles within arm representation of the spinocerebellum.
The Deep Cerebellar Nuclei Are Located Within the White Matter
The deep cerebellar nuclei can be identified in the transverse section through the pons and cerebellum shown in Figure 13–12, from medial to lateral: fastigial, globose, emboliform, and dentate nuclei. Recall that the globose and emboliform nuclei collectively are termed the interposed nuclei. The efferent projections of the deep nuclei course through the inferior and superior cerebellar peduncles.
The fastigial, interposed, and dentate nuclei have differential projections that reflect their functions in maintaining balance, controlling limb movement, and planning movement, respectively. The major targets of the output of the fastigial nucleus are the vestibular nuclei and the reticular formation, two components of the medial descending pathways that control balance and posture. The major targets of the interposed nuclei are the magnocellular division of the red nucleus, where the rubrospinal tract originates and, via the thalamus, the motor cortex. The major targets of the dentate nucleus are the parvocellular division of the red nucleus, which sends its axons to the ipsilateral inferior olivary nucleus via the central tegmental tract (shown at its termination in Figure 13–11A), and, via the thalamus, areas of cortex involved in motor planning. Note that the two divisions of the red nucleus cannot be clearly distinguished. The parvocellular division is much larger than the magnocellular division.
The ascending projections from the deep nuclei course in the superior cerebellar peduncle (Figures 13–12 and, 13–15B4). The superior cerebellar peduncle decussates in the caudal midbrain, at the level of the inferior colliculus (Figure 13–15A, B2). The axons continue rostrally, either synapsing with the two divisions of the red nucleus or passing through the nucleus en route to the motor thalamic nuclei. Collectively, the projections from the deep cerebellar nuclei to the thalamus are termed the cerebellothalamic tract.
The superior cerebellar peduncle is the principal output path of the cerebellum. A. Location of the superior cerebellar peduncle and associated axons from the cerebellum to the thalamus (pale red shading) in relation to the red nucleus and ventrolateral nucleus of the thalamus. B. Transverse myelin-stained sections through the rostral midbrain (B1), caudal midbrain (B2), pons-midbrain junction (isthmus, B3), and rostral pons (B4).
The Ventrolateral Nucleus Relays Cerebellar Output to the Premotor and Primary Motor Cortical Areas
The portion of the thalamus that receives mostly cerebellar input and transmits this information to the motor areas of the frontal lobe, ventrolateral nucleus, is separate from the thalamic sensory nuclei. The ventrolateral nucleus (Figure 13–16) is difficult to identify. One clue that makes identification a bit easier is the presence of the thalamic fasciculus. This band of myelinated fibers contains axons of the cerebellothalamic tract as well as axons of the basal ganglia projection to the thalamus (see Chapter 14).
Myelin-stained coronal section through the ventrolateral nucleus. The inset shows the plane of section.
The ventrolateral nucleus is large and has many component divisions that have distinctive connections, primarily with the frontal lobe but also to the parietal lobe. The interposed and dentate nuclei project to the part of the ventrolateral nucleus that relays information mostly to the primary motor cortex (area 4) and the premotor cortex (lateral area 6). In addition, the dentate nucleus projects to other parts of the ventrolateral nucleus that project to posterior parietal cortex and the medial dorsal thalamus, which transmits information to the prefrontal cortex. The projections from the dentate nucleus interdigitate with but do not overlay the terminations from the interposed nuclei.
The Cerebellum Is Important for Many Nonmotor Functions
Transneuronal viral tracing studies in the monkey have revealed extensive connections between the dentate nucleus and diverse regions of the prefrontal and posterior parietal cortex, basically, nonmotor areas. These projections originate from the dentate nucleus. Routing through the thalamus, the projections target several regions within the prefrontal cortex and posterior parietal cortex. Whereas cerebellar damage in humans produces characteristic motor signs, as described earlier, damage of the posterior lobe can result in cognitive and affective changes. The projections of the cerebellum to prefrontal and posterior parietal cortex in monkey help to explain these nonmotor functions in the human. Also important for the nonmotor cerebellar functions are the descending corticopontine projections from cerebral cortical regions for cognition and affect (eg, Figure 13–7; discussed further below). In the monkey, only about 40% of the dentate nucleus is devoted to motor system connections. This leaves an intriguingly large portion of the nucleus for nonmotor connections and functions. Considering the increased complexity of the human brain, the nonmotor functions of the cerebellum—and the interplay between these functions and movement control—will very likely be an important direction for clinical and basic studies in the future.
The Corticopontine Projection Brings Information From Diverse Cortical Areas to the Cerebellum for Motor Control and Higher Brain Functions
Cerebral cortical regions to which the deep cerebellar nuclei project, via the thalamus, in turn project back to the cerebellum via the corticopontine projection (Figure 13–7). This forms a "closed loop," in which a particular functional region of the cerebellum, for example the hand control zone of the spinocerebellum, projects to an area of the cerebral cortex involved in the same function. We will see a similar predominantly closed loop organization for the basal ganglia (Chapter 14). There is little evidence for the alternative "open loop" organization, in which a cerebellar functional region communicates with cortical areas serving a different function.
In the human, diffusion tensor imaging (DTI; see Figure 2–7) has revealed that the densest of the corticopontine projections arise from the frontal lobe (Figure 13–17), which includes the primary motor cortex (area 4), the premotor areas (area 6) (see Figure 10–8), and the prefrontal association cortex. Additional projections also arise from association cortex in the parietal, occipital, and temporal lobes and from parts of the limbic cortical areas (which play important roles in emotions; see Chapter 16). Also using DTI, the topographic organization of the axons in the human basis pedunculi can be elucidated. Surprisingly, the largest region of the basis pedunculi contains descending axons from nonmotor areas (Figure 13–17). This amplifies what was discussed earlier, that the nonmotor functions of the cerebellum are likely to be very important.
The corticopontine projection originates from most areas of the cerebral cortex, whereas the corticospinal projection originates only from the premotor (yellow), primary motor (dark gray-blue), and somatic sensory (light gray-blue) cortical areas (A). Part B shows schematically the locations of the descending projections in the basis pedunculi from the various cortical areas. The inset in B shows the somatotopic organization of the corticopontine projection in the basis pedunclui based on diffusion tensor imaging (DTI) data in humans. (From Ramnani N, Behrens TE, Johansen-Berg H, et al. The evolution of prefrontal inputs to the cortico-pontine system: diffusion imaging evidence from Macaque monkeys and humans. Cereb Cortex. 2006;16:811-818.)