Anatomy of the cerebellum

On gross inspection, three lobes can be distinguished in the cerebellum: the flocculonodular lobe, the anterior lobe (rostral to the "primary fissure"), and the posterior lobe (dorsal to the "primary fissure"). The latter two can be further divided in a midline cerebellar vermis and lateral cerebellar hemispheres.

Figure 3: Cerebellum and surrounding regions; sagittal view of one hemisphere. A: Midbrain. B: Pons. C: Medulla. D: Spinal cord. E: Fourth ventricle. F: Arbor vitae. G: Tonsil. H: Anterior lobe. I: Posterior lobe.

Figure 4: Schematic representation of the major anatomical subdivisions of the cerebellum. Superior view of an "unrolled" cerebellum, placing the vermis in one plane.

The cerebellum can also be divided in three parts based on both phylogenetic criteria (the evolutionary age of each part) and on functional criteria (the incoming and outgoing connections each part has and the role played in normal cerebellar function). From the phylogenetically oldest to the newest, the three parts are:

Much of what is understood about the functions of the cerebellum stems from careful documentation of the effects of focal lesions in human patients who have suffered from injury or disease or through animal lesion research.

As explained in more detail in the Function section, the cerebellum differs from most other brain areas in that the flow of neural signals through it is almost entirely unidirectional: there are virtually no backward connections between its neuronal elements. Thus the most logical way to describe the cellular structure is to begin with the inputs and follow the sequence of connections through to the outputs.

The four deep nuclei of the cerebellum are the dentate, emboliform, globose, and fastigii nuclei and they act as the main centers of communication, sending and receiving information to and from specific parts of the brain. In addition, these nuclei receive both inhibitory and excitatory signals from other parts of the brain which in turn affect the nuclei's outgoing signals.[7](The globose and the emboliform nuclei make up the interposed nucleus).

Figure 5: Microcircuitry of the cerebellum. Excitatory synapses are denoted by (+) and inhibitory synapses by (-). MF: Mossy fiber. DCN: Deep cerebellar nuclei. IO: Inferior olive. CF: Climbing fiber. GC: Granule cell. PF: Parallel fiber. PC: Purkinje cell. GgC: Golgi cell. SC: Stellate cell. BC: Basket cell.

Figure 6: Confocal micrograph from mouse cerebellum expressing green-fluorescent protein in Purkinje cells

The cytoarchitecture (cellular organization) of the cerebellum is highly uniform, with connections organized into a rough, three-dimensional array of perpendicular circuit elements. This organizational uniformity makes the nerve circuitry relatively easy to study.

There are three layers to the cerebellar cortex; from outer to inner layer, these are the molecular, Purkinje, and granular layers. The function of the cerebellar cortex is essentially to modulate information flowing through the deep nuclei. The microcircuitry of the cerebellum is schematized in Figure 5. Mossy and climbing fibers carry sensorimotor information into the deep nuclei, which in turn pass it on to various premotor areas, thus regulating the gain and timing of motor actions. Mossy and climbing fibers also feed this information into the cerebellar cortex, which performs various computations, resulting in the regulation of Purkinje cell firing. Purkinje neurons feed back into the deep nuclei via a potent inhibitory synapse. This synapse regulates the extent to which mossy and climbing fibers activate the deep nuclei, and thus control the ultimate effect of the cerebellum on motor function. The synaptic strength of almost every synapse in the cerebellar cortex has been shown to undergo synaptic plasticity. This allows the circuitry of the cerebellar cortex to continuously adjust and fine-tune the output of the cerebellum, forming the basis of some types of motor learning and coordination. Each layer in the cerebellar cortex contains the various cell types that comprise this circuitry.

This outermost layer of the cerebellar cortex contains two types of inhibitory interneurons: the stellate and basket cells. It also contains the dendritic arbors of Purkinje neurons and parallel fiber tracts from the granule cells. Both stellate and basket cells form GABAergic synapses onto Purkinje cell dendrites.

The middle layer contains only one type of cell body—that of the large Purkinje cell. Purkinje cells are the primary integrative neurons of the cerebellar cortex and provide its sole output. Purkinje cell dendrites are large arbors with hundreds of spiny branches reaching up into the molecular layer (Fig. 6). These dendritic arbors are flat—nearly all of them lie in planes—with neighboring Purkinje arbors in parallel planes. Each parallel fiber from the granule cells runs orthogonally through these arbors, like a wire passing through many layers. Purkinje neurons are GABAergic—meaning they have inhibitory synapses—with the neurons of the deep cerebellar and vestibular nuclei in the brainstem. Each Purkinje cell receives excitatory input from 100,000 to 200,000 parallel fibers. Parallel fibers are said to be responsible for the simple (all or nothing, amplitude invariant) spiking of the Purkinje cell.

Purkinje cells also receive input from the inferior olivary nucleus via climbing fibers. A good mnemonic for this interaction is the phrase "climb the other olive tree", given that climbing fibers originate from the contralateral inferior olive. In striking contrast to the 100,000-plus inputs from parallel fibers, each Purkinje cell receives input from exactly one climbing fiber; but this single fiber "climbs" the dendrites of the Purkinje cell, winding around them and making a large number of synapses as it goes. The net input is so strong that a single action potential from a climbing fiber is capable of producing a "complex spike" in the Purkinje cell: a burst of several spikes in a row, with diminishing amplitude,[8] followed by a pause during which simple spikes are suppressed.

Just underneath the Purkinje layer are the Lugaro cells whose very long dendrites travel along the boundary between the Purkinje and the granular layers.

The innermost layer contains the cell bodies of three types of cells: the numerous and tiny granule cells, the slightly larger unipolar brush cells[9] and the much larger Golgi cells. Mossy fibers enter the granular layer from their main point of origin, the pontine nuclei. These fibers form excitatory synapses with the granule cells and the cells of the deep cerebellar nuclei. The granule cells send their T-shaped axons—known as parallel fibers—up into the superficial molecular layer, where they form hundreds of thousands of synapses with Purkinje cell dendrites. The human cerebellum contains on the order of 60 to 80 billion granule cells, making this single cell type by far the most numerous neuron in the brain (roughly 70% of all neurons in the brain and spinal cord, combined). Golgi cells provide inhibitory feedback to granule cells, forming a synapse with them and projecting an axon into the molecular layer.

The local field potentials of the neocortex and cerebellum oscillate coherently at (6–40 Hz) in awake behaving animals.[10] These appear to be under the control of output from the cerebral cortex.[11] This output would be mediated by a pathway from layer 5/6 neurons in the neocortex through that project either to the pons or the inferior olive. If through the pons this would go to mossy fibers that synapse with granule and Golgi neurons with the granule cells then targeting Purkinje neurons via their excitatory parallel fibers. If the inferior olive it would go via excitatory climbing fiber inputs to Purkinje neurons.[11] These return this output back to the cerebral cortex through the ventrolateral thalamus completing the loop.

The corticopontocerebellar pathway is the largest pathway associated with the cerebellum. Arising in the cerebral cortex these fibers first terminate ipsilaterally in the pontine nuclei. Then the fibers decussate and form the middle cerebellar peduncle, terminating in the cerebellar cortex as mossy fibers. This pathway transmits signals that inform the cerebellum about the movement in progress and the upcoming movement. This helps the continuous adjustment of motor activity.[12]

The initiation of the movement is relayed to cerebellum via the corticoreticulocerebellar pathway. Those synapse ipsilaterally in the reticular formation, then via the inferior and middle peduncles into the cerebellar vermis.[12]

The motor cortex and somatosensory cortex projects onto the ipsilateral inferior and accessory olivary nuclei, then forming the olivocerebellar tract. Cortico-olivary fibers synapse bilaterally in the inferior olivary nucleus. The order is preserved in the olivocerebellar tract projections onto the ‘body maps’ in the contralateral cerebellar cortex. Under resting conditions in animal experiments, groups of olivary neurons discharge synchronously at 5 to 10 Hz (impulses/s). In the cerebellar cortex, the response of Purkinje cells takes the form of complex spikes.[13]

The cerebellum send its projections back to the cerebral cortex via the Cerebellothalamic tract.

The cerebellar lateral expansion, or the neocerebellum, may be associated with cognitive functions, and it is anatomically linked with the lateral prefrontal cortex. It shows greatest activity during speech, with a one-sided predominance consistent with a possible linkage (via the thalamus) with the motor speech area.[13]

When lesions occur in the association areas linked to the cerebellum by corticopontocerebellar fibres, the cognitive affective syndrome may occur. This results in cognitive defects in the form of diminished reasoning power, inattention, grammatical errors in speech, poor spatial sense, and patchy memory loss.[13]

Figure 7: The three major arteries of the cerebellum: the SCA, AICA, and PICA

Figure 8: Illustration showing regions supplied by the three cerebellar arteries.

Three arteries supply blood to the cerebellum (Fig. 7): the superior cerebellar artery (SCA), anterior inferior cerebellar artery (AICA), and posterior inferior cerebellar artery (PICA).

The SCA branches off the lateral portion of the basilar artery, just inferior to its bifurcation into the posterior cerebral artery. Here, it wraps posteriorly around the pons (to which it also supplies blood) before reaching the cerebellum. The SCA supplies blood to most of the cerebellar cortex, the cerebellar nuclei, and the superior cerebellar peduncles.[14]

The AICA branches off the lateral portion of the basilar artery, just superior to the junction of the vertebral arteries. From its origin, it branches along the inferior portion of the pons at the cerebellopontine angle before reaching the cerebellum. This artery supplies blood to the anterior portion of the inferior cerebellum, the middle cerebellar peduncle, and to the facial (CN VII) and vestibulocochlear nerves (CN VIII). Obstruction of the AICA can cause paresis, paralysis, and loss of sensation in the face; it can also cause hearing impairment. Moreover, it could cause an infarct of the cerebellopontine angle. This could lead to hyperacusia (dysfunction of the stapedius muscle, innervated by CN VII) and vertigo (wrong interpretation from the vestibular semi-circular canal's endolymph acceleration caused by alteration of CN VIII).

The PICA branches off the lateral portion of the vertebral arteries just inferior to their junction with the basilar artery. Before reaching the inferior surface of the cerebellum, the PICA sends branches into the medulla, supplying blood to several cranial nerve nuclei. In the cerebellum, the PICA supplies blood to the posterior inferior portion of the cerebellum, the inferior cerebellar peduncle, the nucleus ambiguus, the vagus motor nucleus, the spinal trigeminal nucleus, the solitary nucleus, and the vestibulocochlear nuclei.

There is considerable variation in the size and shape of the cerebellum in different vertebrate species. It is generally largest in cartilaginous and bony fish, birds, and mammals, but somewhat smaller in reptiles. The large paired and convoluted lobes found in humans are typical of mammals, but the cerebellum is generally a single median lobe in other groups, and is either smooth or only slightly grooved. In mammals, the neocerebellum is the major part of the cerebellum by mass, but in other vertebrates, it is typically the spinocerebellum.[15]

In amphibians, lampreys, and hagfish the cerebellum is little developed; in the latter two groups it is barely distinguishable from the brain-stem. Although the spinocerebellum is present in these groups, the primary structures are small paired nuclei corresponding to the vestibulocerebellum.[15]