Introduction· ‘Cerebellum’ AKA ‘little brain’ = component ofextrapyramidal motor control systems that regulate intentional (voluntarymovement)· Key roles: initiation and coordination ofmultijoint movements and posture, calibration of movements.· Active in: balance, motor execution, planning.· Fast movements become automated through ‘motorlearning’.· Movements of patients with cerebellar lesions =dysynergic and dysmetric, and show·intentiontremor. Gross anatomy· 10% brain volume but over 50% total neurones inCNS.
· Dorsal thin sheet of cortex characterised byfolia, transverse fissures = 10 lobules.· Midline vermis sends outputs to brainstemstructures contributing to ventromedial descending pathways.· Lateral cerebellar hemispheres relay tostructures involved in lateral descending pathways.· Somatotopic organisation: multiplerepresentations of the same body part exist in different locations in thecerebellum (e.g.
Vermis and paravermis) Lesion studies andthe functional subdivisions· The functional and involvement of the different divisionsof the cerebellum can be used to understand their different functions· Vestibulocerebellum= oldest part of cerebellum, which appears evolutionary, first in fish. o Involved in the orientation of the head and bodyfor balance and posture, as well as eye movements. ?o Inputs: flocculonodular lobe (FNL) reveivesdirect input from 1 ? sensory afferents of the vestibular system (e.g.Semicircular canals – only sesnory system that inputs directly to cerebellum).Also receives 2 ? afferents from the vestibular nuclei in the medulla.
?o Outputs: flocculus to fastigial nucleus and vestibularnucleus (ie goes back) -> medial and lateral vestibulospinal tracts -> neckand back muscles = posture and balance. Outputs also to ocular motor nuclei =vestibular-ocular reflex (VOR)o Lesion here leads to characteristic ataxic gait.Wide stance, irregular walking rhythm, and defects in vestibular reflex movementssuch as postural adjustment in response to vestibular input. ?· Spinocerebellum:controls axial and limb musculature.
?o Inputs: sensory and motor cortex, spinocererebellartracts (neck + trunk, ?limbs), inferior olivary nucleus. ?o Outputs: ?§ 1: Vermis-> fastigial nucleus -> ventromedial brainstem descending systems(vestibulo-, reticulo, medial corticospinal tracts vie thalamocortical relays).§ Lesions of medial zone of spinocerebellumdestroy the fastigial nucleus and this the medial descending tracts receive nocerebellar input = abnormal control of axial and girdle antigravity muscles, nocalibration = cannot stand or walk. § 2: Paravermis-> interposed nucleus -> dorsolateral brainstem descending systems(rubro- and lateral corticospinal tracts).§ Lesions of intermediate zone of spinocerebellumdestroy the interposed nucleus = lateral descending tracts receive nocerebellar input = abnormal control of distal limb muscles, no calibration =disruption of reaching movements, actions tremor (3-5Hz).
?· Cerebrocerebellum:involved in the planning and timing of precise movements (motor planning) o Input: cortex via the pons (80% of allcorticofugal fibres are corticopontine). ?o Output: purkinje neurones from lateralcerebellar cortex -> dentate nucleus -> VL ?thalamus-> premotor and motor cortices. ?- ExEv: lesions studies show delaysin intiation of multijoint movements and irregularities in timing of movementcomponents, e.g. reach and grab. o Recordings from primates = dentae nucleus neuronesfire 100ms before movement starts, before neurones in either primary motorcortex or interposed nuclei, which are more directly concerned with theexecution of movement itself. Hore et al used localised dentate cooling toinactivate early output.
Seen to delay onset of movement, but as movement waseventually initiated, dentate nucleus is not absolutely necessary forinitiation. ?o Sasaki et al (1993): implanted electrodes torecord field potentials in cortex. Cooling of the dentate nucleus ipsilateralto moving hand reversible increased reaction time. By shifting probe todifferent distances from nucleus, noted various decreases in cooling effect. ?o Cerebrocerebellum also has purely cognitivefunctions: the dentate nucleus is particularly important in acquiring andprocessing sensory information for complex spatial and temporal judgements,which are essential for complex motor actions and sequences of movements. o Ivry & Keele: medial cerebellar lesions onlyinterfered with accurate execution of the response, whereas lateral cerebellarlesions interfered with timing of serial events. This timing defect was was notjust motor.
Also affected the patients’ ability to judge elapsed time in purelymental or cognitive tasks. o Patient damaged in right cerebellum (blockedPICA) could not learn a word-association task. Circuitry andcytoarchitecture o Cerebellar cortex = simple 3-layered structureconsisting of only 5 types of neurones:§ Inhibitory (GABA): stellate, basket, purkinje,golgi neurones.§ Excitatory (Glu): granule cells ?o Molecular Layer: contains:§ Cell bodies of stellate and basket cells§ Axons of excitatory granule cells (calledparallel fibres)§ Dendrites of inhibitory purkinje cells (PCs -perpendicular to parallel fibres) ?o Purkinje Cell Layer: single layer of Purkinjecell bodies. There are large (50-80um) with fanlike dendritic arborisations thatextend up to molecular layer. Axons project into underlying white matter todeep cerebellar or vestibular nuclei and provide the output of the cerebellarcortex.
Output is mediated by GABA, so inhibitory: natural response, in face ofexcess movement signals from muscle, is to defend correct limb position. ?o Granular Layer: contains: o Estimated 1011 granule cells number. Small anddensely packed, darkly stained ?nuclei. ?o A few larger Golgi interneurones. ?o Mossy fibres: major source of afferent input tothe cerebellum. Their bulbous ?terminals contact granule cells andgolgi neurones in synaptic complexes = cerebellar glomeruli.o Climbing fibres, which terminate on deep nucleiand purkinje neurones, report error on cerebellum calibration and informcerebellum of unexpected stimuli.
Simple Spiking inpurkinje output cells: Mossy Fibre input · Mossy fibres originate from spinal cord andbrainstem nuclei, carrying sensory information. Terminate on granulardendrites. · Convergence = glutamatergic axons of granulecells (parallel fibres) excite large numbers of purkinje neurones in same transverseplane.· Each PC receives input from up 1 200,000parallel fibres from GC, each of which collects inputs from many mossy fibres. · Convergence -> summation and brief excitatorypostsynaptic potential that generates a classic Na/K AP = simple spike.
· PC fires at rate of 20 – 50 Hz. ?· Each PC tunes to particular source or type ofinput. Tonic nature of simple spike allows for more precise encoding ofinformation because frequency can be modulated by sensory and motor inputs. ?Complex spiking inPCs: climbing fibre input ?· Climbing fibre axons originate from neurones incontralateral inferior olivary nucleus, carrying somatosensory, visual, orcerebral cortical information. ?· Each CF contacts 1 – 10 PCs, but each PC receivesinput from only a single CF. ?· The high specific connectivity of CF systemcontrasts with the massive convergence and divergence of mossy and parallelfibres. · Arrangements reflect the type of informationcarried by the different fibre inputs:?- Mossy fibres = broad information?-Climbing fibres = unexpected stimuli which must be dealth with rapidly and ?specifically.
?· CFs have extremely powerful synaptic effects onpurkinje neurones, as they have powerful efficacy.· Each AP in a CF (1-10Hz) generates a prolongedvoltage gated calcium conductance in the soma and dendrites of the postsynapticPC = large EPSP = prolonged depolarisation that produces a complex spike. ?· Therefore: CF activation = high-frequency burstof spikes = complex spike = represents critical signal for operation of thecerebellar cortex, conveying both timing information and triggering synapticplasticity. ?· Sensory stimuli/movement encoded by climbingfibre elicit only 1/2 complex spikes per second – such low frequencies cannotby themselves carry substantial information about the magnitude of naturalstimuli or behaviour. ?· Despite this low frequency, CFs alter cerebellaroutput (complex spikes open Ca2+ channels in PCs) by modulating synaptic effectof parallel fibre input to PCs in 2 ways: · Slightly reduce the strength of parallel fibreinput to PC (so reduce efficacy of mossy fibre input).· Activity in CFs can induce selective LTD insynaptic strength of parallel fibres that are active concurrently.
· Marr-Albus-Ito theory: motor learning: CFsreport ‘error’, effectively teaching ?PCs of the set of parallel fibres towhich they should become less responsive.?- During a movement, CFsprovide error signals that would depress parallel ?fibresthat are active concurrently, to suppress incorrect movements and allow correctmovements to emerge. As this continues over time , a more appropriate patternof activity would emerge as flawed central commands would increasingly besuppressed· Vestibulo-ocular reflex: a coordinated responsethat maintains eyes on a fixed target ?when the head is rotated. In thisshort-latency reflex, motion of head sensed in vestibular labyrinth.
Initiateseye movements in the opposite direction in order to maintain image in the sameposition on retina.