FUNCTIONAL DIVISIONS OF THE CEREBELLUM

Functionally speaking, the cerebellum can be divided into a body, with inputs mainly from the spinal cord and pontine nuclei, and a flocculonodular lobe, which has strong afferent and efferent connections with the vestibular nuclei (Fig. 20.4). The body is subdivided into a series of regions dominated by their spinal or pontine inputs. The anterior lobe, simple lobule, pyramis and biventral lobules are the main recipients of spinal and trigeminal cerebellar afferents. Pontocerebellar input dominates in the folium, tuber and uvula, and throughout the entire hemisphere, including those regions that receive afferents from the spinal cord.

Fig. 20.4 The flattened cerebellar surface and cerebellar nuclei. The transverse lobular organization of the afferent spino-, ponto- and vestibulocerebellar connections of the cortex is shown, together with the longitudinal zonal organization of the efferents from vermis and hemispheres to the cerebellar and vestibular nuclei.

The mediolateral subdivision of the cerebellum into vermis and hemispheres represents a functional subdivision that is closely related to its output. In mammals, the increase in the size of the cerebellar hemispheres parallels the development of the cerebral cortex, and reflects the importance of the corticopontocerebellar input and of the efferent projections of the cerebellar hemispheres (through the dentate, emboliform and globose nuclei) to the thalamus and thence to the cerebral cortex.

CEREBELLAR NUCLEI

Laterally, on either side within the white matter core, are four cerebellar nuclei. These are the dentate, emboliform, globose and fastigial nuclei. The dentate nucleus, which is located most laterally and is by far the largest, is the only nucleus easily visible to the naked eye (Fig. 20.1). It has the form of an irregularly folded sheet of neuronal cell bodies, with a medially directed hilum through which pass a mass of fibres mainly derived from dentate neurones and which form the bulk of the superior cerebellar peduncle. The emboliform and globose nuclei lie medial to the dentate and are equated to the nucleus interpositus (interposed nucleus) in lower species; the emboliform and globose nuclei may sometimes be referred to as the anterior and posterior interposed nuclei, respectively. Their efferent fibres join the superior cerebellar peduncle. The fastigial nucleus lies next to the midline, bordering on the roof of the fourth ventricle. A large proportion of the efferent fibres that leave this nucleus decussate within the cerebellar white matter and subsequently constitute the uncinate fasciculus, which passes dorsal to the superior cerebellar peduncle to enter the contralateral vestibular nuclei. Uncrossed fastigiobulbar fibres enter the vestibular nuclei by passing along the lateral angle of the fourth ventricle, and some fibres of the fastigial nucleus ascend in the superior cerebellar peduncle.

CEREBELLAR PEDUNCLES

Three pairs of peduncles connect the cerebellum with the brain stem (see Ch. 19; Fig. 20.5).

Fig. 20.5 Dissection of the left cerebellar hemisphere and its peduncles.

The middle cerebellar peduncle is the most lateral and by far the largest of the three. It passes obliquely from the basal pons to the cerebellum and is composed almost entirely of fibres that arise from the contralateral basal pontine nuclei, with a small addition from nuclei in the pontine tegmentum.

The inferior cerebellar peduncle is located medial to the middle peduncle. It consists of an outer, compact fibre tract, the restiform body, and a medial, juxtarestiform body. The restiform body is a purely afferent system; it receives the posterior spinocerebellar tract from the spinal cord and the trigeminocerebellar, cuneocerebellar, reticulocerebellar and olivocerebellar tracts from the medulla oblongata. The juxtarestiform body is mainly an efferent system; it is made up almost entirely of efferent Purkinje cell axons from the vestibulocerebellum, on their way to the vestibular nuclei, and uncrossed fibres from the fastigial nucleus. It also contains primary afferent fibres travelling in the vestibular nerve and secondary afferent fibres from the vestibular nuclei. The crossed fibres from the fastigial nucleus pass dorsal to the superior cerebellar peduncle and enter the brain stem as the uncinate fasciculus at the border of the juxtarestiform and restiform bodies.

The superior cerebellar peduncle contains all of the efferent fibres from the dentate, emboliform and globose nuclei and a small fascicle from the fastigial nucleus. Its fibres decussate in the caudal mesencephalon, on their way to synapse in the contralateral red nucleus and thalamus. The anterior spinocerebellar tract reaches the upper part of the pontine tegmentum before looping down within this peduncle to join the spinocerebellar fibres entering through the restiform body.

CEREBELLAR CORTEX

Although the human cerebellum makes up approximately one-tenth of the entire brain by weight, the surface area of the cerebellar cortex, if unfolded, would be about half that of the cerebral cortex. The great majority of cerebellar neurones are small granule cells, so densely packed that the cerebellar cortex contains many more neurones than the cerebral cortex. Unlike the cerebral cortex, where a large number of diverse cell types are arranged differently in different regions, the cerebellar cortex contains a relatively small number of different cell types, which are interconnected in a highly stereotyped way. As a consequence, all regions of the cerebellar cortex look similar in histological sections.

The elements of the cerebellar cortex possess a precise geometric order, which is arrayed relative to the tangential, longitudinal and transverse planes in individual folia. The cortex contains the terminations of afferent ‘climbing’ and ‘mossy’ fibres, five varieties of neurone (granular, stellate, basket, Golgi and Purkinje), neuroglia and blood vessels.

There are three main layers: molecular, Purkinje cell and granular (Fig. 20.6). The main circuit of the cerebellum involves granule cells, Purkinje cells and neurones in the cerebellar nuclei. Granule cells receive the terminals of the mossy fibre afferents (i.e. all afferent systems except the olivocerebellar fibres). The axons of the granule cells ascend to the molecular layer, where they bifurcate into parallel fibres, which are so called because they are oriented parallel to the transverse fissures and perpendicular to the dendritic trees of the Purkinje cells on which they terminate. Purkinje neurones are large and are the sole output cells of the cerebellar cortex. Their axons terminate in the cerebellar nuclei and in the vestibular nuclei. In addition to the dense array of parallel fibres, the dendritic trees of Purkinje cells receive terminals from climbing fibres which originate from neurones in the inferior olivary nucleus. The cerebellar cortex thus receives two distinct types of input: olivocerebellar climbing fibres, which synapse directly on Purkinje neurones, and mossy fibres, which connect to the Purkinje cells via granular neurones, whose axons are the parallel fibres.

Fig. 20.6 The general organization of the cerebellar cortex. A single folium has been sectioned vertically, both in its longitudinal axis (right part of diagram) and transversely.

Both parallel and climbing fibres excite the Purkinje cells, but they differ greatly in their firing characteristics and their effect on them. Purkinje cell axons inhibit their target neurones in the cerebellar nuclei; the latter project to motor control centres in the brain stem and cerebrum. The stellate, basket and Golgi cells are inhibitory interneurones and connect the cortical elements in complex geometrical patterns.

The molecular layer is approximately 300–400 μm thick. It contains a sparse population of neurones, dendritic arborizations, non-myelinated axons and radial fibres of neuroglial cells. Purkinje cell dendritic trees extend towards the surface and spread out in a plane perpendicular to the long axis of the cerebellar folia. Purkinje cell dendrites are flattened. The lateral extent of the Purkinje cell dendrites is some 30 times greater in the transverse plane than it is in a plane parallel to the cerebellar folia. Parallel fibres are the axons of granule cells, the stems of which ascend into the molecular layer where they bifurcate at T-shaped branches. The two branches extend in opposite directions as parallel fibres along the axis of a folium. Parallel fibres terminate on the dendrites of the Purkinje cells and Golgi cells, which they pass on their way, and on the basket and stellate cells of the molecular layer. Dendritic trees of Golgi neurones reach towards the surface. Unlike the flattened dendritic tree of the Purkinje cell, Golgi cell dendrites span the territory of many Purkinje neurones longitudinally as well as transversely. These dendrites receive synapses from parallel fibres. Some Golgi cell dendrites enter the granular layer, where they contact mossy fibre terminals. The cell bodies of Golgi neurones lie below, in the superficial part of the granular layer. The molecular layer also contains the somata, dendrites and axons of stellate neurones (which are located superficially within the molecular layer) and of basket cells (whose somata lie deeper within the molecular layer). Climbing fibres, the terminals of olivocerebellar fibres, ascend through the granular layer to contact Purkinje dendrites in the molecular layer. Radiating branches from large epithelial (Bergmann) glial cells give off processes that surround all neuronal elements, except at the synapses. Their conical expansions join to form an external limiting membrane at the surface of the cerebellum.

The Purkinje cell layer contains the large, pear-shaped somata of the Purkinje cells and the smaller somata of Bergmann glia. Clumps of granule cells and occasional Golgi cells penetrate between the Purkinje cell somata.

The granular layer (Fig. 20.6) is about 100 μm thick in the fissures and 400–500 μm on foliar summits. There are approximately 2.7 million granular neurones per cubic millimetre. It has been estimated that the human cerebellum contains a total of 4.6 × 10¹⁰ granule cells, and that there are 3000 granule cells for each Purkinje cell.

In summary, the granular layer consists of the somata of granule cells and the initial segment of their axons; dendrites of granule cells; branching terminal axons of afferent mossy fibres; climbing fibres passing through the granular layer en route to the molecular layer; and the somata, basal dendrites and complex axonal ramifications of Golgi neurones. Cerebellar glomeruli are synaptic rosettes consisting of a mossy fibre terminal that forms excitatory synapses upon the dendrites of both granule cells and Golgi cells.

Of the five cell types to be described, the first four are inhibitory, liberating γ-aminobutyric acid (GABA), and the fifth is excitatory, liberating L-glutamate. Figure 20.7 summarizes their main connections.

Fig. 20.7 The main intrinsic connections of the cerebellar cortex.

Purkinje cells have a specific geometry, which is conserved in all vertebrate classes (Fig. 20.6). They are arranged in a single layer between the molecular and granular layers. Individual Purkinje cells are separated by about 50 μm transversely and 50–100 μm longitudinally. Their somata measure approximately 50–70 μm vertically and 30–35 μm transversely. The subcellular structure of the Purkinje cell is similar to that of other neurones. One distinguishing feature is subsurface cisterns, often associated with mitochondria, which are present below the plasmalemma of somata and dendrites and may penetrate into the spines. The cisterns are intracellular calcium stores which are important links in the second messenger systems of the cell.

One, sometimes two, large primary dendrites arise from the outer pole of a Purkinje cell. From these an abundant arborization, with several orders of subdivision, extends towards the surface. Branches of each neurone are confined to a narrow sheet in a plane transverse to the long axis of the folium. Proximal first- and second-order dendrites have smooth surfaces with short, stubby spines, and are contacted by climbing fibres. Distal branches show a dense array of dendritic spines, which receive synapses from the terminals of parallel fibres. Inhibitory synapses are received from basket and stellate cells and from the recurrent collaterals of Purkinje cell axons, which contact the shafts of the proximal dendrites. The total number of dendritic spines per Purkinje neurone is in the order of 180,000.

The axon of a Purkinje cell leaves the inner pole of the soma and crosses the granular layer to enter the subjacent white matter. The initial axon segment receives axo-axonic synaptic contacts from distal branches of basket cell axons. Beyond the initial segment, the axon enlarges, becomes myelinated, and gives off collateral branches. The main axon ultimately forms a plexus in one of the cerebellar or vestibular nuclei. The recurrent collateral branches end on other Purkinje cells and on basket and Golgi neurones.