Introduction

Phylogenetically, the initial development of the cerebellum (in fish) took place in relation to the vestibular labyrinth. With development of quadrupedal locomotion, the anterior lobes (in particular) became richly connected to the spinal cord. Assumption of the erect posture and achievement of a whole new range of physical skills have been accompanied by the appearance of massive linkages between the posterior lobes and the cerebral cortex. In general, cerebellar connections with the labyrinth, spinal cord, and cerebral cortex are arranged such that each cerebellar hemisphere is primarily concerned with the coordination of movements on its own side.

The gross anatomy of the cerebellum is described briefly in Chapter 3, where it may be reviewed at this time.

Functional Anatomy

Phylogenetic and functional aspects can be combined (to an approximation) by dividing the cerebellum into strips, as shown in Figure 25.1. The median strip contains the cortex of the vermis, together with the fastigial nucleus in the white matter close to the nodule (Figure 25.2). This strip is the vestibulocerebellum; it has two-way connections with the vestibular nucleus. It controls the responses of that nucleus to signals from the vestibular labyrinth. The fastigial nucleus also projects to the gaze centers of the brainstem (Ch. 24).

Figure 25.1 Zonation of cerebellum. The central nuclei are represented separately.

Figure 25.2 Transverse section of lower pons and cerebellum showing the position of the central and vestibular nuclei.

A paramedian strip, the spinocerebellum, includes the paravermal cortex and the globose and emboliform nuclei (Figure 25.2). The two nuclei are together called the interposed nucleus. The spinocerebellum is rich in spinocerebellar connections. It is involved in the control of posture and gait.

The remaining, lateral strip is much the largest and takes in the wrinkled dentate nucleus (Figure 25.2). This strip is the pontocerebellum, because it receives a massive input from the contralateral nuclei pontis. It is also called the neocerebellum, because the nuclei pontis convey information from large areas of the cerebral neocortex (phylogenetically the most recent). The neocerebellum is uniquely large in the human brain.

Microscopic Anatomy

The structure of the cerebellar cortex is uniform throughout. From within outward, the cortex comprises granular, piriform, and molecular layers (Figure 25.3).

Figure 25.3 Cerebellar cortex. (A) Cell layers. (B) Afferent systems. (C) Internuncial neurons. (D) Efferent system.

The granular layer contains billions of granule cells, whose somas are only 6–8 µm in diameter. Their short dendrites receive so-called mossy fibers from all sources except the inferior olivary nucleus. Before reaching the cerebellar cortex, the mossy fibers, which are excitatory in nature, give off collateral branches to the central nuclei.

The axons of the granule cells penetrate to the molecular layer where they divide in a T-shaped manner to form parallel fibers. The parallel fibers run parallel to the axes of the folia. They make excitatory contacts with dendrites of Purkinje cells.

The granular layer also contains Golgi cells (see later).

The piriform layer consists of very large Purkinje cells. The fan-shaped dendritic trees of the Purkinje cells are the largest dendritic trees in the entire nervous system. The fans are disposed at right angles to the parallel fibers.

The dendritic trees of Purkinje cells are penetrated by huge numbers of parallel fiber axons of granule cells, each one making successive, one per cell, synapses upon dendritic spines of about 400 Purkinje cells. Not surprisingly, stimulation of small numbers of granule cells by mossy fibers has a merely facilitatory effect upon Purkinje cells. Many thousands of parallel fibers must act simultaneously to bring the membrane potential to firing level.

Each dendritic tree also receives a single climbing fiber from the contralateral inferior olivary nucleus. In stark contrast to the one-per-cell synapses of parallel fibers, the olivocerebellar fiber divides at the Purkinje dendritic branch points and makes thousands of synaptic contacts with dendritic spines. A single threshold pulse applied to one climbing fiber is sufficient to elicit a short burst of action potentials from the client Purkinje cell. Climbing fiber effects on Purkinje cells are so powerful that, for some time after they cease firing, the synaptic effectiveness of bundles of parallel fibers is reduced. In this sense, the Purkinje cells remember that they have been excited by olivocerebellar fibers.

The axons of the Purkinje cells are the only axons to emerge from the cerebellar cortex. Remarkably, they are entirely inhibitory in their effects. Their principal targets are the central nuclei. They give off collateral branches also, mainly to Golgi cells.

The molecular layer is almost entirely taken up with Purkinje dendrites, parallel fibers, supporting neuroglial cells, and blood vessels. However, two sets of inhibitory neurons are also found there, lying in the same plane as the Purkinje cell dendritic trees. Near the cortical surface are small, stellate cells, and close to the piriform layer are larger, basket cells. Both sets are contacted by parallel fibers, and they both synapse on Purkinje cells. The stellate cells synapse upon dendritic shafts whereas the basket cells form a ‘basket’ of synaptic contacts around the soma, as well as forming axo-axonic synapses upon the initial segment of the axon. A single basket cell synapses upon some 250 Purkinje cells.

The final cell type in the cortex is the Golgi cell, whose dendrites are contacted by parallel fibers and whose axons divide extensively before synapsing upon the short dendrites of granule cells. The synaptic ensemble that includes a mossy fiber terminal, granule cell dendrites, and Golgi cell boutons is known as a glomerulus (Figures 25.4, 25.5).

Figure 25.4 A synaptic glomerulus. +/− indicates excitation/inhibition.

Figure 25.5 Ultrastructure of a synaptic glomerulus. The arrows point to six axodendritic synapses between a mossy fiber (MF) and granule cells. GN, nucleus of granule cell.

(Reproduced with permission from Pennese, E. (1994) Neurocytology. Fine Structure of Neurons, Nerve Processes and Neuroglial Cells. New York: Thieme.)

Spatial effects of mossy fiber activity (Figure 25.6)

As already noted, cerebellar afferents other than olivocerebellar ones form mossy fiber terminals after giving off excitatory collaterals to one of the deep nuclei. The afferents excite groups of granule cells, which in turn facilitate many hundreds of Purkinje cells. Along most of the beam of excitation, known as a microzone, the Purkinje cells begin to fire, and to inhibit patches of cells in one of the deep nuclei. At the same time, weakly facilitated Purkinje cells along the edges of the microzone are shut off by stellate and basket cells. As a result, the beam of excitation is sharply focused. The excitation is terminated by Golgi cell inhibition of the granule cells that initiated it. Powerful excitation will last longer because highly active Purkinje cells inhibit underlying Golgi cells through their collateral branches.

Figure 25.6 Scheme of effects of mossy fiber activity.

1 Mossy fiber stimulating a granule cell (Gr).

2 Beam of parallel fiber activity follows simultaneous activation of many granule cells.

3 Activation of on-line Purkinje cells (P1) results in selective inhibition of neurons within the appropriate central cerebellar nucleus.

4 Activation of stellate (S) and basket cells (B) inhibits off-line Purkinje cells (P2).

5 Golgi cells (Go) terminate granule cell activity.

6 Intense on-line activity can be sustained by inhibition of Golgi cells by Purkinje cells.

Representation of Body Parts