Internal Structure · 243 5

Internal Structure

Although the cerebellum accounts for only about 10% of the brain by weight, it contains more than 50% of all the brain’s neurons. The neurons of the cerebellum are located in the gray matter of the highly convoluted cerebellar cortex and in the four deep cerebellar nuclei on either side (see below).

Cerebellar Cortex

The cerebellar cortex is composed of three layers (Fig. 5.3). Proceeding from the outermost inward, these layers are:

Molecular layer (stratum moleculare). This layer consists mainly of cellular processes,ofwhichthemajorityaregranulecellaxons—parallelfibers,seebelow— and Purkinje cell dendrites. A few neurons are found among the fibers (stellate cells, basket cells, Golgi cells), which function as inhibitory interneurons.

Pukinje cell layer (stratum ganglionare). This thin layer contains nothing but the large cell bodies of the Purkinje cells, arranged side by side in rows. The elaborate, highly branched dendritic trees of these cells are directed outward into the molecular layer, where the dendritic tree of each individual Purkinje cell lies in a plane perpendicular to the long axis of the folium. The Purkinje cell axons are the only efferent fibers leaving the cerebellar cortex. They project mainly to the deep cerebellar nuclei and release the inhibitory neurotransmitter GABA (γ-aminobutyric acid). Efferent fibers from the cortex of the vestibulocerebellum bypass the deep cerebellar nuclei and project directly to sites outside the cerebellum.

Granulecelllayer(stratumgranulosum).Thislayerconsistsalmostentirelyofthe denselypackedcellbodiesofthesmallgranulecells,whichaccountformorethan 95% of all cerebellar neurons. The axons of these cells are mainly found in the molecular layer, where they travel along individual folia as parallel fibers and form synapses with the perpendicularly oriented dendritic trees of the Purkinje cells(approximately200 000parallelfibersformsynapseswithasinglePurkinje cell). The cerebellar granule cells are glutamatergic and are the only neurons of the cerebellar cortex that exert an excitatory influence on their target cells.

Afferent Input to the Cerebellar Cortex

The afferent input to the cerebellar cortex is mainly derived from the ipsilateral vestibular nuclei (a small part, in fact, comes directly from the vestibular organ,

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Internal Structure · 245 5

fibers and climbing fibers give off important collaterals to the deep cerebellar nuclei on their way to the cortex.

In view of the fact that both the mossy fibers and the granule cells (and thus the overwhelming majority of synapses in the cerebellum) are glutamatergic, it is not surprising that the administration of glutamate antagonists causes a marked worsening of cerebellar function in patients with cerebellar lesions.

Cerebellar Nuclei

A horizontal section of the cerebellum reveals four deep nuclei within each cerebellar hemisphere (see Fig. 5.5). The fastigial nucleus (“roof nucleus”) is found most medially, in the roof of the fourth ventricle. It receives most of its afferent fibers from the Purkinje cells of the flocculonodular lobe (vestibulocerebellum). Its efferent fibers travel directly to the vestibular nuclei (fastigiobulbar tract) (Fig. 5.5) or cross to the opposite side of the cerebellum and then continue to the reticular formation and the vestibular nuclei (uncinate fasciculus).

Lateral to the fastigial nucleus, one finds two smaller nuclei, the globose nucleus (usually divided into two or three subnuclei) and the emboliform nucleus. Both of these nuclei receive afferent input from the cortex of the paravermian zone and vermis (spinocerebellum) and send efferent fibers to the contralateral red nucleus (Fig. 5.5).

The largest of the cerebellar nuclei, the dentate nucleus, occupies a lateral position in the deep white matter of each cerebellar hemisphere. Its afferent input comes mainly from the cortex of the cerebellar hemispheres (cerebrocerebellum), and, to a lesser extent, from the cortex of the paravermian zone. Its efferent fibers travel by way of the superior cerebellar peduncle to the contralateral red nucleus and thalamus (ventral lateral nucleus, VL) (Fig. 5.5). The thalamus is the site of a synaptic relay, with further projection to the motor areas of the cerebral cortex (Brodmann areas 4 and 6) (Fig. 6.4, p. 266).

Afferent and Efferent Projections of the Cerebellar Cortex

and Nuclei

Synaptic transmission within the cerebellum follows a uniform scheme (Fig. 5.4): the cerebellar afferent pathways project to the cerebellar cortex and, through collateral fibers, to the deep cerebellar nuclei. In the cortex, afferent information is processed in a complex polysynaptic pathway that eventually converges onto the Purkinje cells. The Purkinje cells, in turn, transmit the results of this processing to the deep cerebellar nuclei, in the form of inhibitory, GABAergic impulses. In the deep nuclei, integrative processing of both primary

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Further afferent fibers from the monoaminergic raphe nuclei travel by way of the middle cerebellar peduncle to the cerebellum.

Superior Cerebellar Peduncle

Efferent pathways. The superior cerebellar peduncle (brachium conjunctivum) contains most of the cerebellar efferent fibers. These fibers originate in the deep cerebellar nuclei and project mainly to the following structures:

The contralateral thalamus (ventral lateral and centromedian nuclei, Figs. 6.4 and 6.6, p. 266ff.)

The contralateral red nucleus

The reticular formation

Efferent fibers to the thalamus. Efferent fibers in the superior cerebellar peduncle traveling to the thalamus arise mainly in the dentate nucleus (cerebrocerebellum). After a synaptic relay in the thalamus, further fibers ascend to the motor and premotor cerebral cortex, which, in turn, projects back to the pontine nuclei by way of the corticopontine tract. A long regulatory loop is thus created, traveling from the cerebral cortex to the pontine nuclei, cerebellar cortex, dentate nucleus, thalamus, and finally back to the cortex (Figs 5.5 and 5.6).

Efferent fibers to the red nucleus and reticular formation. A further regulatory circuit comprises the so-called triangle of Guillain and Mollaret, traveling from the red nucleus by way of the central tegmental tract to the olive, then to the cerebellum and back to the red nucleus (Fig. 5.7). The cerebellum influences spinal motor function by way of fibers traveling from the red nucleus and reticular formation down into the spinal cord (cf. Fig. 3.5, p. 62).

Afferent pathways. One of the few afferent pathways in the superior cerebellar peduncle is the anterior spinocerebellar tract, which terminates in the same area (spinocerebellum) as the posterior spinocerebellar tract. Both convey proprioceptive impulses from the periphery, i.e., from muscle spindles, Golgi tendon organs, and joint receptors.

Fibers from the tectum travel to the cerebellar vermis in the tectocerebellar tract, which occupies a medial position in the superior cerebellar peduncle, at its transition to the superior medullary velum. These fibers convey auditory information from the inferior colliculi, and probably also visual information from the superior colliculi.

Topography of Cerebellar Afferent Pathways

Each half of the cerebellum is responsible for motor function on the ipsilateral half of the body. Some of the efferent fiber systems are doubly crossed: thus,

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