The human cerebellum is located at the base of the
brain, with the large mass of the
cerebrum above it, and the portion of the
brainstem called the
pons in front of it. It is separated from the overlying cerebrum by a
layer of tough dura mater called the
cerebellar tentorium; all of its connections with other parts of the brain travel through the pons. Anatomists classify the cerebellum as part of the
metencephalon, which also includes the pons; the metencephalon in turn is the upper part of the
rhombencephalon or "hindbrain". Like the cerebral cortex, the cerebellum is divided into two hemispheres; it also contains a narrow midline zone called the
vermis. A set of large folds are conventionally used to divide the overall structure into ten smaller
lobules. Because of its large number of tiny
granule cells, the cerebellum contains more
neurons than the rest of the brain put together, but it only takes up 10% of total brain volume. The cerebellum receives nearly 200 million input fibers; in contrast, the
optic nerve is composed of a mere one million fibers. The bulk of the cerebellum is made up of a very tightly folded layer of
gray matter, the
cerebellar cortex. It has been estimated that if the human cerebellar cortex could be completely unfolded it would give rise to a layer of neural tissue about 1 meter long and 10 centimeters wide—a total surface area of 500-1000 square cm, all packed within a volume of 100-150 cubic cm. Underneath the gray matter of the cortex lies
white matter, made up largely of myelinated nerve fibers running to and from the cortex. The white matter of the cerebellum is known as the
arbor vitae (tree of life) because of its branched, tree-like appearance. Embedded within this are four
deep cerebellar nuclei. The cerebellum can be divided according to three different criteria: gross anatomical, phylogenetical, and functional.
Gross anatomical divisions 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.
Phylogenetic and functional divisions 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.
Cellular anatomy 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.
Deep nuclei 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.(The globose and the emboliform nuclei make up the
interposed nucleus).
Cortical layers . 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.
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.
Molecular layer 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.
Purkinje layer 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, 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.
Granular layer The innermost layer contains the cell bodies of three types of cells: the numerous and tiny
granule cells, the slightly larger
unipolar brush cells 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.
Relationship with cerebral cortex The
local field potentials of the neocortex and cerebellum oscillate coherently at (6–40 Hz) in awake behaving animals. These appear to be under the control of output from the cerebral cortex. 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. 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. 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. 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.
Variations among vertebrates 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. 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. ==Peduncles==