Cerebellum

What appearance does the cerebellum have?

laminated

What does the vermis separate?

the lateral hemispheres

What does the primary fissure separate?

the anterior from the posterior lobe

Whats does the horizontal fissure separate?

the superior from the inferior surface

What does the posterolateral fissure separate?

the posterior lobe from the flocculonodular lobe

How are the nuclei organised?

• outer cortex with deep cerebellar nuclei

  • main output zone where most processing within cerebellar cortex

What are the functional divisions of the cerebellum?

• vestibulocerebellum

• spinocerebellum

• cerebrocerebellum

What is the input to vestibulocerebellum?

• vesitbular inputs from primary sensory afferents and visual inputs

• flocculonodualr love and vestibular nuclei, some via fastigial

What is the output of the vestibulocerebellum?

• flocculus to fastigial nucleus and vestibular nuclei

• medial and lateral vestibulospinal tracts to neck and back muscles

• outputs to ocular motor nuclei

Function of vestibulocerebellum?

• primitive part

• balance via axial and proximal limb muscles

• control and coordination of eye movements

Damage to the vestibulocerebellum

• nystagmus

  • poor or absent smooth pursuit and abnormal vestibulo-occular reflex

What does the spinocerebellum consist of?

the vermis and paravermis

What are the inputs and outputs to the vermis?

What are the inputs and outputs of the paravermis?

What is the function of the spinocerebellum?

• posture and axial musculature

• regulates body and limb movements

What does damage to the spinocerebellum do?

• ataxia

• impaired motor coordination

• action tremor

What is the cerebrocerebellum consisted of?

• the lateral parts of the hemispheres

• most recent and much larger relative to cerebellum comapred to monkeys etc

What is the input to the cerebrocerebellum?

the cerebral cortex

What is the ouput of the cerebrocerebellum?

dentate nucleus which projects via the thalamus to motot, premotor, parietal and prefrontal cortices

Function of cerebrocerebellum?

• planning and executing movement

• cognitive functions eg language processing

What are cerebellar peduncles?

white matter axon bundles that connect these regions

What is the cytoarchitexture of the cerebellar cortex like?

• molecular layer

• single cell purkinje layer

• granule cell layer

• then subcortical white matter

Where do climbing fibres originate from?

the inferior olive

What do the mossy fibre cells do?

major afferent input - comprise input from all other brain regions excpet IO

How the circuitry seems to work?

• excitatory input from purkinje cells from climbing fibres and granule cells

• climbing from IO and granule from mossy fibre

• purkinje cell has output to cerebellar nuclei

• all other cells mentioned are in the layers of the cerebellar cortex

Circuitry full explained:

• two types of afferent input:

  • mossy fibres

    • these originate from many sources eg spinal cord and synapse with granule cells in granular layer

    • granule cells to parallel fibres to purkinje

  • climbing fibres

    • these originate from the IO nucleus

    • synapse directly with Purkinje

• purkinje cells are the only output neurons

  • axons project to deep cerebellar nuclei

  • they are GABAergic

What features are there in the electrical properties of a Purkinje cell?

• simple spikes and complex spikes

• seen using electrode and patch clamp

What do parallel fibres do?

• granule cell axons ascend from the granule layer into molecular and bifurcate into parallel fibres

• pass through dendrites of 450 POurkinje cells and forms synaptic contacts with dendritic spines of 300 Purkinje cells

  • Eccles et al, 1967

• form SIMPLE SPIKES

What do climbing fibres do?

• axons from the contralateral IO neurons

• each mature Purkinje cell innervated by one climbing fibre

• numerous synaptic contacts meaning large EPSP causing COMPLEX SPIKE (calcium dependent)

What pattern and activity does the cerebellar cortex have?

patterned molecular expression and heterogeneity in PC activity

What is a large function of the cerebellum?

• compares the intended movement and actual movement

• can predict the sensory consequences of commands and act as feedback system

What can looking at Purkinje and deep nuclear cells for example with wrist flexion and extension firing tell us?

• shows coordination of ongoing movement

• constantly tracking movements and updating it

• modulating depending on the change of movement

What is there evidence for PC simple spike doing?

• motor learning and coordination

• losing the beat: contribution of Purkinje cell firing dysfunction to disease and its reversal

What are climbing fibres viewed as the source of?

• instructing signal and regulating cerebellar dependent motor learning

Long term depression also related – complex spike activity

What is a critical mechanism required for cerebellar motor learning?

• long term depression of the synaptic input from parallel fibres

  • stimulate climbing, amplitude of parallel going down, activity in Purkinje decrease

Look at study on next slide to find more info and references

Basic description of LTD - may not be super correct?

• coincident activity of input to Purkinje fibres from parallel fibres and climbing fibres

• intracellular calcium rises in the Purkinje cell which triggers molecular pathways and parallel fibre synapse is weakened

• less excitation of Purkinje - less inhibition of DCN and stronger output from cerebellum

• encodes motor error correction

What else is critical for motor learning?

• PF-PC LTP

• climbing fibres play critical role in bi-directional plasticity at these synapses

• Coesmans, Weber, De Zeeuw and Hansel, 2004

Another reference:

D’Angelo – the organisation of plasticity in the cerebellar cortex from synapses to control

(really not necessary actually)

What can the cerebellum do with eyes?

• contribute to experience-dependent modification of saccadic eye movements

Reference on slide STILL CANT FIND BUT LOOKS USEFUL

What is the study which looks at learning adaptation using prism goggles?

Martin et al, 1996

Other examples of cerebellar function beyond movement control?

• emotion processing, word comprehension, language processing

What are two references for how cerebellum function extends beyond motor control?

• Schmahmann and Sherman (1998)

  • describes the cerebellar cognitive affective syndrome and how this is characterised by deficits in executive function, linguistic processing, spatial cognitiion and affect regulation

  • especially with lesions of the posterior and vermis

• Wang, Kloth and Badura (2014)

  • looks at the connection with autism and social interaction specifically proposing that sensitive-period disruption of such internal brain communication can account for autism’s key features

What are typical symptoms of cerebellar disease?

• inaccuracy in range and direction (dysmetria)

• inability to stabilise

• irregular pattern of repeated movements

Symptoms of cerebellar ataxia?

-          Posture and gait deficits

-          Lack of coordination of limbs

-          Oculomotor and speech deficits – dysarthria

-          Cog deficits and subtle autonomic signs

-          Inability to learn complex motor skills

What is spinocerebellar ataxia?

• neurogenetive disorders affecting cerebellum and connections leading to progressive problems with coordination

• degeneration of pathways connecting spinal cord and cerebellum

• symptoms eg unsteady gait, poor coordiantion etc

What causes essential tremor?

-          Cerebellar cortex circuitry alterations

-          Lack of Purkinje neurons?

-          More info needed

-          Ibrahim et al, 2021

SEARCH UP CIRCUITRY + DEPRESSION, READING, LOOK AT STUDIES MENTIONED

Research shows how cerebellum involved in eye saccades through lesioning of monkeys

Takagi et al, 1998

• the oculomotor vermis plays a critical role both in the immediate on-line and in the short-term adaptive control of pursuit

Showed specifically the uvula and vermal pyramid important for smooth eye movements by looking at 28 patients with cerebellar damage, comparing different patients.

Baier et al, 2009