The Cerebellar Neuronal Circuit

Published Date: 02 Nov 2017

The cerebellum is a functional region of the brain located towards the anterior portion of the brain underneath occipital and temporal aspects of the cerebral cortex. The cerebellum has a substantial mass of the cerebral cortex located at its apex, whilst its hind portion is masked by the pons, a constituent region of the brainstem. The cerebellum is encapsulated by a layer of dura matter isolating it from the overlaying cerebrum. The cerebellum is compartmentalised into two hemispheres with a minor medial zone known as the vermis which connects the two hemispheres. The majority of the cerebellum is composed of a very compact layer of gray matter known as the cerebral cortex, within the gray matter of the cerebral cortex lies a region of white matter known as the arbor vitae. Morphologically, the arbor vitae is composed of an infrastructure of glial cells and myelinated axons projecting to and from the Cerebellar cortex. The cerebellum has until recently been thought of as the aspect of the brain which initiates movement due to the fact that lesioning of cerebellar cortex results in a lack of the expression of voluntary movement (Jones & Powell, 1970), however recent research into the cerebellums structure and function has found that it in fact modulates the motor commands of descending upper motor pathways in order to fine tune movement to in turn make them more precise and modality specific (Huttenlocher, 2002). This essay shall discuss the structure and function of the cerebellum in relation to its functional subdivisions and neuronal composition, it will also discuss the cerebellar circuits properties of regulation and look at the cerebellar circuits role within the nervous system. It is important to understand that the cerebellar neuronal circuit cannot be understood in terms of a single unit of neural anatomy, the cerebellar circuit is instead an integral component of the cerebellum and its surrounding neural architecture which as a whole plays host to a variety of neural structures each with a specific type of neural composition and associative connection (Marr, 1969).

The cerebellum is composed of two key aspects: the deep cerebellar nuclei and the cerebellar cortex, the deep cerebellar nuclei are the single solitary source of output from the cerebellum. The deep cerebellar nuclei are contained within the arbor vitae which is cloaked by the gray matter of the cerebellar cortex. The cerebellar cortex is divided into three principal subsidiary aspects via two major fissures running mediolaterally along the cortex. (Hansson, Rönnbäck, Persson, Lowenthal, Noppe, Alling, & Karlsson, 1984.). The posterolateral fissure segregates the flocculonodular lobe from the corpus cerebelli, whilst the primary fissure divide the corpus cerebelli into the anterior lobe and posterior lobe respectively. (Hansson et al, 1984). The cerebellum is also separated sagitally into three regions known as the vermis located medially, the intermediate zone which lies laterally to the vermis and the lateral hemispheres which are located laterally to the intermediate zone (Borges & Lewis, 1983).

Functional anatomy of the deep cerebellar nuclei and Cerebellar peduncles

It is postulated that the deep cerebellar nuclei located in the arbor vitae are the principal districts of the brain from which the outputs from the cerebellum are derived due to the fact that lesions within the deep cerebellar nuclei results in the almost certain eradication of conditioned behavioural responses (Clark, McCormick, Lavond & Thompson, 1984). The arbor vitae contains within it four types of deep cerebellar nuclei (see Figure 1): The fastigial nucleus, obtains afferent inputs from the vermis and projects efferent outputs to the vestibular nuclei via the inferior cerebellar peduncle. The interposed nuclei is consisted of the globose nuclei and emboliform nuclei, it is located laterally to the fastigial nuclei where it receives afferent input from the anterior lobe whilst projecting its output to the red nucleus via the superior cerebellar peduncle. The dentate nucleus is the most lateral of the four deep cerebellar nuclei, it receives afferent input from the pre-motor cortex via the pontocerebellar system, it projects its efferent output to the ventrolateral thalamus via the superior cerebellar peduncle and the red nucleus (Purves, Augustine, Fitzpatrick, Katz, LaMantia, McNamara & Williams, 2001).. The vestibular nuclei originate in the vestibulospinal tracts and known to be located outside the arbor vitae, they are in fact located in the medulla, however due to their functional and morphological similarities with the other deep nuclei they are considered to be one in the same. The vestibular nuclei receive input from the flocculonodular lobe and vestibular labyrinth and project out to differing motor nuclei (Purves et al, 2001)

Inputs and outputs from the deep cerebellar nuclei in to the cerebellum are both augmented and facilitated by inputs from the inferior olive via: the inferior cerebellar peduncle, the middle cerebellar peduncle and the superior cerebeller peduncle. Both the inferior and middle cerebellar peduncle contain afferent fibres, however the superior cerebellar peduncle contains both afferent and efferent fibres (Purves et al, 2001). As a result all inputs to the cerebellum are principally expressed through the inferior and middle cerebellar peduncle, whereas all outputs are expressed principally through the superior cerebellar peduncle.

Functional subdivisions of the cerebellum and their properties of neuronal connection

Anatomically speaking, the cerebellum is divided into three functional subdivisions (see Figure 1): the vestibulocerebellum, the spinocerebellum and the cerebrocerebellum. Each of the three functional subdivisions makes connections with a differing aspects of the nervous system in order to carry out its functions.

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Figure 1: Posterior view of the functional subdivisions of the cerebellum and the

deep cerebellar nuclei. From: Nelson (2010)

The vestibulocerebellum is a prominent aspect of the coordination of vestibular reflexes as well as in mechanisms of balance such as postural modulation (Voogd, Gerrits & Ruigrok, 1996). The vestibulocerebellum receives various types of inputs from differing aspects of the nervous system: it attains vestibular input from the semicircular canals and from the vestibular nuclei (Voogd et al, 1996), it also attains visual input from the superior colliculi and visual cortex through which it modulates eye movement (Pierrot-Deseilligny, Milea & Müri, 2004). The midline area of the anterior and posterior lobes forms the basis of the spinocerebellum, it receives significant input from the spinocerebellar tract which is involved in the transmission of information pertaining to limb and joint position. It projects out to the reticular formation, medial pathway and extra-pyramidal tract. Noticeably the spinocerebellum projects fibres to the deep cerebellar nuclei that consequently project to the cerebral cortex and brainstem. This projection between the deep cerebellar nuclei, cerebral cortex and brainstem in turn provides a mechanism of modulation in regards to the downward motor systems. In essence the spinocerebellum functions to provide a sensory map of the position of limbs in real time in order to correctly identify and postulate future directional position and movement in relation to a particular course of voluntary movement (Voogd et al, 1996).

The cerebrocerebellum is the latter most region of the cerebellum. The cerebrocerebellum acquires input solely from the cerebral cortex via the pontine nuclei. This exclusive input from the cerebral cortex into the cerebrocerebellum is known as the cortico-ponto-cerebellar pathway. The cerebrocerebellum has two major output devices; the ventrolateral thalamus and the red nucleus. This output to the ventrolateral thalamus allows for the innervation of motor areas of the pre-motor cortex and primary motor region of the cerebellar cortex. The cerebrocerebellum primarily functions to aid in the perceptual reasoning involved in the planning and timing stages of movement future movement (Voogd et al, 1996).

Neural circuitry; a basis for the modulation and regulation of the cerebellum and cerebellar cortex.

Neural circuits are made up of three key neuronal subunits: afferent neurons, efferent neurons and interneuron's. Afferent neurons or sensory neurons carry sensory information from external stimuli toward the central nervous system, afferent neurons are primarily responsible for the conversion of external stimuli to analogous internal stimuli which is then processed by the integral regions of the brain. Neurons which transport information away from the central nervous system are known as efferent neurons or motor neurons, more specifically efferent neurons transport information away from the central nervous system to effector organs or a specifically targeted effector cell. Interneuron's are neither afferent nor efferent, interneuron's form connections between multiple neurons and as a result only participate in localized aspects of neuronal circuits.

Afferent pathways project to the cerebellar cortex via a specific type of neuron known as the Purkinje cell however, this projection is not direct (see Figure 2). Neurons derived from the pontine nuclei receive input from the cerebral cortex which is then in turn conveyed to the contralateral cerebellar cortex.

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Figure 1: Ultrastructural map of the Purkinje cell circuit, the foundation of the cerebellar neuronal circuit. From: Mann (2012)

Axons originating from the pontine nuclei are known as mossy fibres, due to the appearance of their synaptic terminal (Hamlyn, 1962). Mossy fibres branch to form excitatory synaptic swellings known as rosettes in the granule cell layer of the cerebral cortex, this causes granule cells axons to divide in the molecular layer to form a unique form of axon known as a parallel fibre. In the molecular layer parallel fibres bifurcate at right angles to form excitatory synapses with the dendritic spines of Purkinje cells. Dendritic spines of Purkinje cells extend upward into the molecular layer to form the Purkinje layer, here in the molecular layer the dendrites of Purkinje cells branch at right angles to the course of nearby parallel fibres (Purves et al, 2001). Due to the ultrastructure of the Purkinje cells dendritic spines and the ascending parallel fibres, Purkinje cells can receive a large volume of excitatory input each time a mossy fibre fires. Purkinje cells are directly regulated by climbing mossy fibres which emerge from the inferior olive. Climbing fibres in turn modulate movement in that they regulate the efficacy of the mossy-parallel-fibre connection between the parallel fibres and the proximally located Purkinje cells (Purves et al, 2001).

Purkinje cells once stimulated with then broadcast to the deep cerebellar nuclei, as in essence Purkinje cells are the only forms of output leaving the cerebellar cortex. However, the projections to deep cerebellar nuclei is inhibitory in nature due to the fact that Purkinje cells are GABAergic, thus excitatory projections into the deep cerebellar nuclei come from the collaterals of the mossy and climbing fibres which are both excitatory in nature (Gauck, & Jaeger, 2000).. Thus the inhibition of deep cerebellar nuclei through Purkinje cells seeks to act as a mechanism of regulation in terms of the levels of excitation the deep cerebellar nuclei can experience (Gauck, & Jaeger, 2000).

The regulation of inhibitory activity of Purkinje cells occurs through interneuron's located on the dendritic spines and the soma of the Purkinje cell. The most prolific use of interneuron's as a means via which the activity of a Purkinje cell can be inhibited is in the ultrastructural system between the soma of Purkinje cells and nearby basket cells ((Byrne, 2007). Purkinje cell activity can also be inhibited by the inhibitory stellate cell, which when excited by parallel fibres emit inhibitory properties upon the Purkinje cell thus inhibiting the excitable activity of the Purkinje cell, this is a mechanism via the potential for excitation can indeed be limited (Andersen, et al, 1964) Golgi cell dendrites found in the molecular layer are also excited by parallel fibres, once Golgi cell dendrites are excited they provide inhibit the mossy-fibre-granule cell relay thus inhibiting the formation that it coming into the cerebellar circuitry. The regulation of signal flow and excitation through the Purkinje and granule cells provides the infrastructure of real-time regulation of movement as well as the long-standing changes in modulation that underlie motor learning (Gilbert, & Thach, 1977). In this way, stellate, Golgi and basket cells modulate and regulate the flow of information coming into the cerebral cortex, more specifically: Golgi cells administer inhibitory feedback that in turn increases the latency of excitation within Purkinje cells (Byrne, 2007). Basket cells deliver lateral inhibition that may moderate the spatial distribution of activity within a Purkinje cell, and we know that Purkinje cells regulate the activity of the deep cerebellar nuclei via the direct excitatory input they receive from the collaterals of innervating mossy and climbing fibres, in turn the regulated output of the cerebellum could be attributed to Purkinje cell circuit (Andersen, Eccles, & Voorhoeve, 1964). This in essence could be one of the primary reasons that systems of motor learning and control are integral aspects of the cerebellar circuit. (Byrne, 2007).

In conclusion, this essay has discussed the cerebellar circuit with particular attention to neuronal ultrastructure and regulation, as well the each neuronal subunits connections both afferent and efferent, the important thing to understand is that the function of the cerebellar neuronal circuit cannot simply be understood it terms of raw composition or the immediate structure to which it make contact or connection with, the function of the cerebellar circuit is better understood in terms of the overall picture, namely the function of cerebellum; which is to co-ordination of fine motor movement of limbs (Voogd et al, 1996), eyes (Pierrot-Deseilligny, Milea & Müri, 2004). Important findings have made pertaining to the necessity of specific functional aspects of the cerebellar neuronal circuit such as the deep cerebellar nuclei and its outputs and inputs into the pre and primary motor cortex (Purves et al, 2001). There is also evidence to suggest that lesioning in this area created deficits in motor control as well the deficits in the ability to regulate body movement (Jones & Powell, 1970). Future research into the area of the structure and function of the cerebellar neuronal circuit should look to expand on the pathological consequences of lesioning in humans as opposed to rats or other forms of lower mammal, perhaps then could we get a true insight as to the functional implications specific forms of neurodegenerative defects and impact on the cerebellar circuits function.