Chapter 13 Cerebellum

The cerebellum, the largest part of the hindbrain, is dorsal to the pons and medulla, and its median region is separated from them by the fourth ventricle. It is joined to the brain stem by three pairs of cerebellar peduncles, which contain afferent and efferent fibres. The cerebellum occupies the posterior cranial fossa, where it is covered by the tentorium cerebelli. It is roughly spherical but somewhat constricted in its median region and flattened; its greatest diameter is transverse. In adults, the weight ratio of cerebellum to cerebrum is approximately 1 : 10; in infants, it is approximately 1 : 20.

The cerebellum is a central part of the major circuitry that links sensory to motor areas of the brain, and it is required for the coordination of fine movement. In health, it provides corrections during movement, which are the bases for precision and accuracy, and it is critically involved in motor learning and reflex modification. It receives sensory information through spinal, trigeminal and vestibulocerebellar pathways and, via the pontine nuclei, from the cerebral cortex and the tectum. Cerebellar output is mainly to those structures of the brain that control movement.

The basic internal organization of the cerebellum is that of a superficial, highly convoluted cortex (a laminated sheet of neurones and supporting cells) overlying a dense core of white matter. The latter contains deep cerebellar nuclei, which give rise to the efferent cerebellar projections. 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; they are 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 that are interconnected in a highly stereotypical way. Consequently, one region of the cerebellar cortex looks very much like another.

Disease processes affecting the cerebellum or its connections lead to incoordination. Movements of the eyes, speech apparatus, individual limbs and balance are usually affected, which results in nystagmus, dysarthria, incoordination and ataxia. Although all these movements become defective in widespread disease of the cerebellum or its connections, topographical arrangements within the cerebellum lead to a variety of clinically recognizable disease patterns. Thus, in cerebellar hemisphere disease, the ipsilateral limbs show rhythmical tremor during movement but not at rest. The tremor increases as the target is approached, so reaching and accurate movements of the arm are especially difficult. Diseases that affect the ascending spinocerebellar pathways or the midline vermis have a disproportionate effect on axial structures, leading to severe loss of balance. Lesions of outflow tracts in the superior cerebellar peduncles result in a wide-amplitude, severely disabling, proximal tremor that interferes with all movements and may even disturb posture, leading to rhythmic oscillations of the head or trunk so that the patient is unable to stand or sit without support. However, although cerebellar lesions may initially cause profound motor impairment, a considerable degree of recovery is possible. There are clinical reports that the initial symptoms of large cerebellar lesions (caused by trauma or surgical excision) have improved progressively over time.

Although the basic structure of the cerebellum and its importance for normal movement have long been recognized, many of the details of how it functions remain obscure. The main goal of this chapter is to describe the known structure and connections of the cerebellum.

External Features and Relations

The cerebellum consists of two large, laterally located hemispheres that are united by a midline vermis (Figs 13.1–13.3). The superior surface of the cerebellum, which would constitute the anterior part of the unrolled cerebellar cortex, is relatively flat. The paramedian sulci are shallow, and the borders between vermis and hemispheres are indicated by kinks in the transverse fissures. The superior surface adjoins the tentorium cerebelli and projects beyond its free edge. The transverse sinus borders the cerebellum at the point where the superior and inferior surfaces meet. The inferior surface is characterized by a massive enlargement of the cerebellar hemispheres, which extends medially to overlie some of the vermis. Deep paramedian sulci demarcate the vermis from the hemispheres. Posteriorly, the hemispheres are separated by a deep vallecula, which contains the dural falx cerebelli. The inferior cerebellar surface lies against the occipital squama. The shape of the surface facing the brain stem is irregular. It forms the roof of the fourth ventricle and the lateral recesses on each side of it, while the cerebellar peduncles define the diamond shape of the ventricle when viewed from behind. Anterolaterally, the cerebellum lies against the posterior surface of the petrous part of the temporal bone.

Fig. 13.1 Horizontal section through the cerebellum and brain stem.

(Courtesy of Dr. G. J. A. Maart.)

Fig. 13.2 Magnetic resonance images of the cerebellum of a 16-year-old girl. A, Sagittal slice. B, Coronal slice. C, Axial slice.

(Courtesy of Drs. J. P. Finn and T. Parrish, Northwestern University School of Medicine, Chicago, toddp@northwestern.edu.)

Fig. 13.3 Terminology of cerebellar lobes and fissures, using a schematic ‘unrolled’ diagram as a frame of reference. A, Unrolled cerebellar cortex. The lobules are labelled by numbers, and the fissures between the wings are listed. B, Cerebellum viewed from above. C, Median sagittal section of cerebellum. The nodules and wings are numbered and listed. D, Cerebellum viewed from below.

The cerebellar surface is divided by numerous curved transverse fissures that separate its folia and give it a laminated appearance. Deeper fissures divide it into lobules. One conspicuous fissure, the horizontal fissure, extends around the dorsolateral border of each hemisphere from the middle cerebellar peduncle to the vallecula, separating the superior and inferior surfaces. Although the horizontal fissure is prominent, it appears relatively late in embryological development and does not mark the boundary between major functional subdivisions of the cortex. The deepest fissure in the vermis is the primary fissure, which curves ventrolaterally around the superior surface of the cerebellum to meet the horizontal fissures. It appears early in embryological development and marks the boundary between the anterior and posterior lobes.

Because the cerebellar cortex has a roughly spherical shape, the true relations between its parts can sometimes be obscured. Thus, the most anterior lobule of the cerebellar vermis, the lingula, lies very close to the most posterior lobule, the nodule. Deep fissures divide the superior vermis into lobules. The lobules of the superior vermis that belong to the anterior lobe are the lingula, central lobule and culmen. The lingula is a single lamina of four or five shallow folia. Its white core is continuous with the anterior medullary velum. It is separated from the central lobule by the precentral fissure. The central lobule and culmen are continuous bilaterally with an adjoining wing (ala) in each hemisphere. The central lobule is separated from the culmen by the preculminary fissure. The culmen (with attached anterior quadrangular lobules) lies between the preculminary and primary fissures.

Between the primary and horizontal fissures are the simple lobule (with attached posterior quadrangular lobules) and the folium (with attached superior semilunar lobules). These two lobule sets are separated by the posterior superior fissure.

From the back forward, the inferior vermis is divided into the tuber, pyramis, uvula and nodule, in that order (see Fig. 13.3C). The tuber is continuous laterally with the inferior semilunar lobules and separated from the pyramis by the lunogracile fissure. The pyramis and attached biventral lobules (containing an intrabiventral fissure) are separated from the uvula and attached cerebellar tonsils by the secondary fissure. Behind the uvula, and separated from it by the median part of the posterolateral fissure, is the nodule. The tonsils are roughly spherical and overhang the foramen magnum on each side of the medulla oblongata.

The nodule and attached flocculi constitute a separate flocculonodular lobe that is separated from the uvula and tonsils by the deep posterolateral fissure. This lobe is richly interconnected with the vestibular nucleus, which is located at the lateral margin of the fourth ventricle.

Functional Divisions

The cerebellum is divided functionally 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. 13.4). 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 in the entire hemisphere, including those regions that receive afferents from the spinal cord.

Fig. 13.4 Diagrams of the flattened cerebellar surface. A, Transverse lobular organization of the afferent spino-, ponto- and vestibulocerebellar connections of the cortex. B, Longitudinal zonal organization of the vermis and hemispheres with 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, a great 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 and interposed cerebellar nuclei and the thalamus) to the cerebral cortex.

Cerebellar Peduncles

Three peduncles connect the cerebellum with the rest of the brain (Figs 13.5, 13.6). 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 arising 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 (Latin for ‘rope-like’) 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. Apart from primary afferent fibres of the vestibular nerve and secondary afferent fibres from the vestibular nuclei, it is made up almost entirely of efferent Purkinje cell axons from the vestibulocerebellum, on their way to the vestibular nuclei, and the uncrossed fibres from the fastigial nucleus. The crossed fibres from the fastigial nucleus, after passing dorsal to the superior cerebellar peduncle, enter the brain stem as the uncinate fasciculus at the border of the juxtarestiform and restiform bodies.

Fig. 13.5 Dissection of the left cerebellar hemisphere and its peduncles.

(Courtesy of Dr. E. B. Jamieson, University of Edinburgh.)

Fig. 13.6 Diagram illustrating the composition of the cerebellar peduncles. A, Dorsal view. B, Lateral view.

The superior cerebellar peduncle contains all the efferent fibres from the dentate, emboliform and globose nuclei and a small fascicle from the fastigial nucleus. It decussates with its opposite number in the caudal mesencephalon, on its 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.

Internal Structure

The white core of the cerebellum branches in diverging medullary laminae, which occupy the central part of the lobules and are covered by the cerebellar cortex. In a sagittal section through the cerebellum, the highly branched pattern of medullary laminae is known as the arbor vitae. The white core consists of the efferents (Purkinje cell axons) and afferents of the cerebellar cortex. Fibres crossing the midline in the white core of the cerebellum and the anterior medullary velum constitute the cerebellar commissure. This consists of an efferent portion, containing decussating fibres from the fastigial nucleus, and an afferent portion, containing fibres of the restiform body and the middle cerebellar peduncle. (In neuroanatomy, the word ‘commissure’ may have two meanings. In one sense, a commissure such as the corpus callosum connects homotopic points on the two sides of the brain. However, in the cerebellum, commissural afferent and efferent fibres are simply crossing the midline. The cerebellum has no callosum-like commissure connecting homotopic points on the two sides.)

Laterally, the medullary laminae merge into a large, central white mass that contains the four cerebellar nuclei: the dentate and the anterior (emboliform) and posterior (globose) interposed and fastigial nuclei (see Fig. 13.4). The dentate nucleus is the most lateral and largest and is an irregularly folded sheet of neurones that encloses a mass of fibres derived mainly from dentate neurones. It resembles a leather purse, the opening of which is directed medially. Fibres stream out through this so-called hilum to form the bulk of the superior cerebellar peduncle. The anterior and posterior interposed and fastigial nuclei lie medial to the dentate nucleus. The anterior interposed nucleus is continuous laterally with the dentate. The posterior interposed nucleus is medial to the anterior nucleus and is continuous with the fastigial nucleus, which is located next to the midline, bordering the fastigium (roof) of the fourth ventricle. Efferent fibres from the interposed nuclei join the superior cerebellar peduncle. A large proportion of the efferent fibres from the fastigial nucleus cross within the cerebellar white matter of the cerebellar commissure. After their decussation, they constitute the uncinate fasciculus (hook bundle), which passes dorsal to the superior cerebellar peduncle to enter the vestibular nuclei of the opposite side (see Fig. 13.6). Uncrossed fastigiobulbar fibres enter the vestibular nuclei by passing along the lateral angle of the fourth ventricle. Some fibres of the fastigial nucleus ascend in the superior cerebellar peduncle.

Cerebellar Cortex

The elements of the cerebellar cortex possess a precise geometrical 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. 13.7). 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 (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 vestibular nuclei. In addition to the dense array of parallel fibres, the dendritic trees of Purkinje cells receive terminals from climbing fibres whose neurones of origin are 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. 13.7 General organization of the cerebellar cortex. A single folium has been sectioned vertically, both in its longitudinal axis (right side of the diagram) and transversely. The two asterisks on the left face indicate recurrent collateral branches of Purkinje cell axons.

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

The molecular layer is approximately 300 to 400 µm thick. It contains a sparse population of neurones, dendritic arborizations, non-myelinated axons and radial fibres of the neuroglial cells. Purkinje cell dendritic trees extend toward 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 approximately 30 times greater in the transverse plane than 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 toward 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, which are 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. At the surface of the cerebellum, their conical expansions join to form an external limiting membrane.

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

The granular layer (see Fig. 13.7) is approximately 100 µm thick in the fissures and 400 to 500 µm thick 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 start 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 on the dendrites of both granule cells and Golgi cells.

Of the five cell types described, the first four are inhibitory, liberating γ-aminobutyric acid (GABA), and the fifth is excitatory, liberating L-glutamate. Figure 13.8 summarizes their main connections.

Fig. 13.8 Diagrammatic representation of the main circuits of the cerebellar cortex. The cortex is indicated by the grey background.

Purkinje cells have a specific geometry that is conserved in all vertebrate classes (see Fig. 13.7). They are arranged in a single layer between the molecular and granular layers. Individual Purkinje cells are separated by approximately 50 µm transversely and 50 to 100 µm longitudinally. Their somata measure 50 to 70 µm vertically and 30 to 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, that are present below the plasmalemma of somata and dendrites and may penetrate into the spines. They are intracellular calcium stores, which are important links in the second messenger systems of the cell.

One or 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 toward 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 approximately 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.

Basket and stellate cells are the neurones of the molecular layer. Their sparsely branched dendritic trees and the ramifications of their axons lie in a plane approximately perpendicular to the long axis of the folium—that is, in the same plane as the Purkinje cell dendritic tree. Stellate cells are located in the superficial molecular layer, and their axons synapse with the shafts of Purkinje cell dendrites. Both stellate and basket cells receive excitatory synapses from parallel fibres passing through their dendritic trees. Basket cells lie in the lower third of the molecular layer. Their somata receive synapses from Purkinje cell recurrent collaterals and from climbing and mossy fibres, as well as from the parallel fibres. Basket cell axons increase in size away from their somata and run deep in the molecular layer just above the Purkinje cells. Continuing for approximately 1 mm, each covers the territories of 10 to 12 Purkinje neurones. Collaterals of the basket cell axons ascend along Purkinje cell dendrites and descend toward Purkinje cell somata and initial axonal segments, forming pericellular networks, or ‘baskets,’ around them. Branches from each basket cell axon also extend in the direction of the long axis of the folium to an additional three to six rows of Purkinje neurones, flanking the axon. It follows that as many as 72 Purkinje cell neurones may receive synapses from a single basket neurone.

Most Golgi cell somata occupy the superficial zone of the granular layer, adjoining the Purkinje cell somata. Their dendrites radiate into the molecular layer. Unlike Purkinje cells, the dendritic trees of Golgi cells are not flattened, appearing much the same in transverse and longitudinal foliar section. In both planes they overlap the territories of several neighbouring Purkinje and Golgi cells. Some Golgi dendrites, however, divide in the granular layer and join cerebellar glomeruli, where they receive excitatory synaptic contacts from mossy fibres. The axon of the Golgi cell arises from the base of the cell body or proximal dendrite and immediately divides into a profuse arborization that extends through the entire thickness of the granular layer. The volume of the territory occupied by the axonal ramifications corresponds approximately to that of its dendritic tree in the molecular layer and it overlaps with the axonal arborizations of adjacent Golgi cells. The main synaptic input to Golgi cell dendrites is from parallel fibres in the molecular layer. Purkinje cell recurrent collaterals and mossy and climbing fibres also terminate on their proximal dendrites and, more sparsely, on their somata.

Each granule cell has a spherical nucleus, 5 to 8 µm in diameter, with a mere shell of cytoplasm containing a few small mitochondria, ribosomes and a diminutive Golgi complex. Granule cells give rise to three to five short dendrites that end in claw-like terminals within the synaptic glomeruli. The fine axons of granule cells enter the molecular layer and branch at a T-junction to form parallel fibres passing in opposite directions over a distance of several millimetres. Terminals located along the parallel fibres give them a beaded appearance and are sites of synapses on the dendrites of Purkinje, stellate, basket and Golgi cells in the molecular layer. Most numerous are the synapses with Purkinje dendritic spines. It has been estimated that 250,000 parallel fibres cross a single Purkinje dendritic tree, although every parallel fibre may not synapse with the dendritic tree it crosses.

Two very different excitatory inputs serve the cerebellar cortex: climbing fibres and mossy fibres. Climbing fibres arise only from the inferior olivary nucleus. Olivocerebellar fibres cross the white matter and enter the granular layer, where they branch to form climbing fibres. Each climbing fibre innervates a single Purkinje cell. There are about 10 times as many Purkinje cells as there are cells in the inferior olive, so each olivocerebellar fibre branches into approximately 10 climbing fibres. Individual climbing fibres pass alongside the soma of a Purkinje cell and then branch to make numerous synapses on the short, stubby spines that protrude from the proximal segments of Purkinje cell dendrites.

Mossy fibres take their origin from the spinal cord, trigeminal, dorsal column and reticular nuclei of the medulla and from the pontine tegmentum and basal pons. Like climbing fibres, they are excitatory, but they contrast sharply in their anatomical distribution and physiological properties. As each mossy fibre traverses the white matter, its branches diverge to enter several adjacent folia. Within each folium, these branches expand into grape-like synaptic terminals (mossy fibre rosettes) that occupy the centre of cerebellar glomeruli.

Noradrenergic and serotoninergic fibres form a rich plexus in all layers of the cerebellar cortex. The aminergic fibres are fine and varicose and form extensive cortical plexuses; their release of noradrenaline (norepinephrine) and serotonin is assumed to be non-synaptic, and their effects are paracrine, involving volumes of tissue. The serotoninergic afferents of the cerebellum take their origin from neurones in the medullary reticular formation, other than the raphe nuclei. The noradrenergic, coeruleocerebellar projection, when active, inhibits Purkinje cell firing not by direct action but by β-adrenergic receptor–mediated inhibition of adenylate cyclase in the Purkinje cells. The presence of dopamine in elements of the cerebellar cortex is still disputed. Cerebellar afferents have been traced from dopaminergic cells in the ventral tegmental area, and dopamine D2 and D3 receptors are present in the molecular layer. A similar plexus of thin, choline acetyltransferase–containing fibres is centred on the Purkinje cell layer. The origin of this cholinergic plexus is not known.

The connections of the cerebellum are organized in two perpendicular planes, corresponding to the planar organization of the cerebellar cortex. Efferent connections of the cortex are disposed in parasagittal sheets or bundles that connect longitudinal strips of Purkinje cells with specific cerebellar or vestibular nuclei. The climbing fibre afferents to a Purkinje cell zone from the inferior olive display a similar zonal disposition. Cerebellar output is organized in modules, with a module consisting of one or more Purkinje cell zones, their cerebellar or vestibular target nucleus and their olivocerebellar climbing fibre input. Modular function is determined by the brain stem projections of the cerebellar or vestibular target nucleus. A general feature of the modular organization of the cerebellum is that GABAergic neurones in the cerebellar nuclei project to the subnuclei of the contralateral inferior olive, which give rise to their respective climbing fibre afferents. These recurrent connections are known as nucleo-olivary pathways.

Mossy fibre afferent systems from precerebellar nuclei in the spinal cord and the brain stem terminate in the granular layer of certain lobules in transversely oriented terminal fields. The transverse lobular arrangement of the mossy fibre afferents is enforced by the transverse orientation of the parallel fibres, which are axons of the granule cells and constitute the second link in the mossy fibre–parallel fibre input of the Purkinje cells. Parallel fibres cross and terminate on Purkinje cells belonging to several successive modules as they course through the molecular layer.

Purkinje cells can be activated in two different ways. Granule cell activity generates simple spikes, which resemble the response of other neurones in the brain, whereas activation by a climbing fibre produces a prolonged depolarization on which several spike-like waves are superimposed. The rate of firing of single and complex spikes also differs markedly. Whereas the Purkinje cell may fire simple spikes at a rate of hundreds per second, complex spikes occur at very low frequencies, seldom more than three or four per second.

Purkinje cell activity is regulated by local Golgi, basket and stellate cells. Like Purkinje cells, Golgi cells have a rich dendritic tree that extends through the molecular layer. Unlike Purkinje cells, the Golgi cell dendrites are not restricted to a plane transverse to the folia, and their axons do not leave the cerebellar cortex. Golgi cells regulate firing by presynaptic inhibition of the mossy fibre afferents, so they act as a governor, or rate limiter, of Purkinje cell activity. Stellate and basket cells synapse directly on Purkinje cells and are powerful inhibitors of their activity.

Structural and Functional Cerebellar Localization

Because the cerebellar cortex is largely uniform in microstructure and microcircuitry, it seems likely that its basic mode of operation is also uniform. The most obvious input for this operation is provided by the mossy fibre afferents, which carry information from all levels of the spinal cord, and specialized sensory and motor information relayed from the cerebral cortex and subcortical motor centres. The most obvious output from the cerebellum is directed at motor systems. Purkinje cells are organized in modules, which are discrete, parallel zones that converge on different cerebellar output nuclei coupled to different motor systems in the brain stem, spinal cord and cerebral cortex. Cerebellar function is therefore determined by temporal and spatial factors (e.g. inhibitory interneurones of the cerebellar cortex), which regulate the access of a particular combination of mossy fibre–parallel fibre inputs to an appropriate output. Plastic changes in the response properties of Purkinje cells, in the form of long-term depression of the parallel fibre–Purkinje cell synapses, may also contribute. Short-term and long-term changes in the response properties of Purkinje cells are under the influence of the climbing fibres.

A double, mirrored localization exists in the anterior and posterior cerebellum (Fig. 13.9). The anterior lobe, simple lobule, pyramis and adjoining lobules of the hemisphere of the posterior lobe all receive branches from the same mossy and climbing fibres and project to the same cerebellar nuclei. The efferent pathways of these regions monitor the activity in the corticospinal tract and in the subcortical motor systems descending from the vestibular nuclei and reticular formation. The inputs to the cerebellum and the outputs from it are organized according to the same somatotopic patterns, but the orientation of these patterns is reversed. The representation of the head is found principally in the simple lobule and caudally in a corresponding region of the posterior lobe. The double representation of the body follows in rough somatotopic order. Vestibular connections of the cerebellum display a similar double representation in the most rostral lobules of the anterior lobe and far caudally in the vestibulocerebellum (Fig. 13.10).