What is the cellular organisation of the cerebellum?

How might
this organisation relate to its function?

Despite accounting for only 10% of the brain's whole weight, the
unconsciously operating cerebellum, the largest region of the hindbrain, contains
approximately half of the total neurons found in the brain. Thought to govern major
aspects of the human neurology such as movement, muscle tone and maintaining
balance, it is also believed to play an influential role in several other areas eg speech,
attention and sensation. It covers the fourth ventricle and consists of two laterally-
located hemispheres joined at the midline by the vermis. Its anchoring to the
brainstem is achieved through three bundles of strong fibres – the inferior, middle
and superior cerebellar peduncles which link to the medulla, pons and midbrain
respectively. When viewing the gross anatomy of the dorsal cerebellum, one would
notice an intricate folding of the surface running transversely, termed folia, between
which fissures of differing depths will lie. Two of these, the primary fissure, located
on the superior aspect of the cerebellum and the posterolateral fissure, located on the
inferior, are essential in the classification of the cerebellum into its appropriate
lobes. The anterior and posterior lobe are distinguished by the primary fissure while
the posterolateral identifies the flocculonodular lobe, comprising the vermis and
minor areas of the hemisphere or flocculus. The arrangement of the separated vermis
and lateral hemispheres also reflects a functional division between these two units.
The vermis concerns output to the brainstem via the ventromedial descending spinal
pathways and thus is important in the musculature of the axial skeleton while the
cerebellar hemispheres act with the cerebral cortex through lateral pathways in
generating our locomotion.
Understanding the cytoarchitecture of the cerebellum begins with discerning
the basic structure of it, which consists of an outer cerebellar cortex composed of
grey matter with an inner white matter core. Not only does one find a multitude of
afferent and efferent fibres projecting to and away from the cortex here but also there
are four pairs of cerebellar nuclei deep within the white matter that are responsible
for the majority of cortical output to brainstem structures. These nuclei, named
fastigial, globose, emboliform and dentate in order from medial to lateral, are located
just above the roof of the 4th ventricle and receive input from extra-cerebellar areas
such as the vestibular nuclei, reticular nuclei, pontine nuclei and spinocerebellar
tracts. In terms of output, the fastigial projects to the vestibular system, the globose
and emboliform to the red nucleus and descending spinal systems and the dentate, the
largest of all four, to the ventral laternal nucleus of the thalamus and ultimately the
motor and premotor cortex.
The structural arrangement of the cortex is mirrored in all regions with three
layers being involved. An inner granular layer containing an abundance of granule
cells, an intermediate Purkinje cell later and an outer molecular layer rich in fibre.
Fibres, which project to the cerebellum, will enter the cerebellar peduncles and then
will travel as climbing fibres if they originate from the inferior olivary nucleus or
mossy fibres, which originate from all other regions, towards the cortex. While the
climbing fibres will project to the Purkinje cells, the mossy fibres target the granule
cells. The latter will branch to folia and then come into synaptic contact with the
granule cells. The axons of these cells will travel to the cortex and enter the
molecular layer bifurcating into two parallel fibres, running perpendicular to the
dendrites of the Purkinje cell. Hence one can see that a single parallel fibre will only
briefly intersect a dendrite however it will encounter many in its path. The parallel
fibres are believed to be responsible for the simple spiking of the Purkinje cell, an all
or nothing impulse which is amplitude invariant. Due to this prolific arrangement of
parallel fibres running adjacent to each other, each Purkinje cell receives excitatory
input from 100,000-200,000 parallel fibres. The Purkinje cell layer, so called because
of their discovery by the Czech neuroanatomist, is unicellular with profuse somata of
the Purkinje neurons. Dendrites of these cells project to the cortical surface reaching
the molecular layer. Arborisations of these dendrites will run flat and be traversed by
many parallel fibres, which provide a source of excitatory input. As mentioned
earlier, climbing fibres exhibit a direct impact on the Purkinje cells in addition to the
indirect effect of the parallel fibres. As a result of the structure of the winding
climbing fibres, a large number of synapses are generated between the climbing fibre
and the Purkinje cell and in contrast to the parallel fibres, a given Purkinje cell will
only receive input from one climbing fibre. Thus a single action potential in a
climbing fibre will result in series of firings with diminishing amplitudes, termed a
complex spike. Other cells, known as Golgi, basket and stellate cells, dictate an
inhibitory impact on the overall potential, modulating it. Other notable characteristics
are that Purkinje axons are the only to leave the cerebellar cortex with most of them
terminating in the deep cerebellar nucleus and GABA is the neurotransmitter used by
this cell suggesting that nearly the entire output of the cerebellar cortex occurs
through inhibition.
When examining the cerebellum in terms of function, it is often subdivided into
three sections, the vestibulocerebellum, spinocerebellum and the cerebrocerebellum,
each one comprising a certain region of the cerebellum and accounting for different
output pathways. The vestibulocerebellum is associated with the flocculonodular
lobe and the fastigial nucleus and is concerned with maintaining balance and
movements of the eye. Thus one can understand why a lesion of this region induces
difficulties of balance and distortion of gait. With input from vestibular nuclei and
semicicular canals as well as a visual component from the superior colliculus and the
visual cortex via the pontine nucleus, this subdivision has efferent Purkinje cells
which will project to the fastigial nucleus and ultimately back to the vestibular nuclei
and reticular formation for the aspect of balance. While vestibular input travels to the
cortex of the ipsilateral flocculonodular lobe, most of the efferents will cross to the
contralateral side of the brainstem.
The spinocerebellum accounts for the vermis and surrounding paravermis with
the globose and emboliform nuclei output. This subdivision controls muscle tone and
posture, playing a major role in our proprioception. A large number of afferents will
travel to the ipsilateral vermis and paravermis including not only dorsal and ventral
spinocerebellar tracts carrying information from receptors on muscles, joint and skin
but also the trigeminal nerve and visual and auditory systems. In terms of
proprioception, the spinocerebellum concerns sensory maps which lock on to the
position of several parts of the body simultaneously thus generating our conception
of where we and all our individual components are relative to us and relative to
space.
Proximal regions of limbs and the trunk are assoicated with the vermis while distal
portions of limbs are governed by intermediate parts of the hemispheres. Efferents
from the spinocerebellum project to the globose, emboliform and occasionally to the
fastigial nucleus. The globose and emboliform nucleu project to the contralateral red
nucleus of the midbrain through the superior cerebellar peduncle where they will
ultimately modulate the activity of the impulse travelling down the descending
rubrospinal tract.
The last subdivision, the cerebrocerebellum, regulates planning movement and
muscle coordination i.e. The speed, force and trajectory of movements by modulation
of descending corticospinal and corticobulbar pathways. Its input arises from the
cerebral cortex, especially the pareietal cortex, through the afferent pathways of
pontocerebellar fibres from the pontine nuclei, located in the basal portion of the
pons. The fibres then cross over and enter the middle cerebellar peduncle terminating
at the cerebrocerebellar cortex. Via the dentate nucleus, the output projects to both
the ventral lateral nucleus of the thalamus and the rubothalamic cells of the red
nucleus of the midbrain follwed by the thalamus, decussating at the caudal midbrain.
The ventral lateral nucleus will project to the cerebral cortex and in particular the
motor cortex situated in the frontal lobe.
One of the most mysterious functions of the cerebellum is its role in motor
learning. Indeed the Marr-Albus theory of motor learning suggests that if a parallel
fibre synapse is active simultaneous with the climbing fibre input to the Purkinje cell,
there will be a degree of synaptic plasticity. The concept of synaptic plasticity,
proposed by Donald Hebb in the 1940s, suggests that the firing of neurons in a
synapse changes the shape or character of the junction in such a way that the
efficiency of the impulse is altered. Indeed long-term potentiation is thought to play a
major role in the formation of memories however with motor learning in the
cerebellum, the process involved is believed to be long-term depression.
Subsequently Ito and his colleagues at the University of Tokyo demonstrated
evidence for the validity of the Marr-Albus theory however the mechanisms of LTD
are still poorly understood. Of paramount importance is the fact that LTD in the
cerebellum only operates upon the simultaneous activity of both the parallel fibres
and the climbing fibres on the Purkinje cells and this results in a less effective
parallel fibre-Purkinje cell synapse (in contrast to the increased effectiveness of
synapses undergoing long-term potentiation). LTD is believed to result
pharmacologically from the internalisation of AMPA receptors in the postsynaptic
cell. Glutamate is the neurotransmitter dictating the excitatory transmission from the
parallel fibre and the AMPA receptor is the protein responsible for propagation of the
impulse by the Purkinje cell.
The cerebellum's importance in maintenance of the human body and its
everyday actions can not be stressed. By simply examining the pathologies that can
affect it, one can observe its significant role in a plethora of activities. Lesions can
result in intention tremor, nystagmus, dysarthria, and ataxia illustrating the wide
range of neurological functions that it overlooks. Whether generating an internal
model of sensorimotor performance, adjusting motor pathways or modulating our
parameters to display our proprioception, the cerebellum still remains an elusive
region of the brain which requires extensive research.