cerebellum: “little brain” cerebellum

CerebellumCerebellum

• The anatomy of the cerebellum and itsThe anatomy of the cerebellum and its gross divisions

• Its principal input and output pathways• Its principal input and output pathways• The organization of the cerebellar

tcortex• Role of climbing vs. mossy fibre inputg y p• The parallel-fibre/Purkinje cell model of

learninglearning• Roles of the cerebellum in motor control

Oct-10 RCM - BMedSci Neuro III 2 of 36

Cortico-cerebellar Premotor,

Sensory motorP t P i t lloop Post. Parietal

Inputs: Sensory –motor cortex, assocation (PPC)assocation (PPC), spinal, vestibular, everything but primary sensory,

Outputs: to all areas it receives from, via thalamus (to cortex)

Cerebellum

( )and red n. (to spine)


Cerebellum: “little brain”


Cerebellum• Massive cortical area, but much simpler

th tthan neo-cortex• Exerts influence on movement via

influence motor and pre-motor cortex • Also connects with reticular formation• Also connects with reticular formation

and spinal cord• Adds coordination, fine control, skill to

basic movement patternsbasic movement patterns• A powerful learning machine


Heavy cortical folding in transverse plane:10 lobes

Deep cerebellar nuclei


Cortical nomenclature

Deep cerebellar nucleiLateral (or dentate)Interposed (interpositus)Interposed (interpositus)

emboliformglobose

Medial (fastigial)


( g )

Cerebellar-nuclear j tiprojections

lateral hemispherelateral hemisphere

intermediate or paravermal interposed

dentate

paravermal

vermal

pfastigial

Ordered projection fromOrdered projection from Purkine cells to “deep cerebellar nuclei”

Also to lateral vestibular nuclei


Thin cortical sheetPurkinje

cellscells

1 mm1 mm

Section though bird b ll tcerebellar cortex

Cajal 1905


Somatotopylateral hemisphere py

B d

intermediate

vermis

anterior lobe Body representations in anterior lobe and in

posterior lobe

anterior lobe and in posterior lobe

Large areas of

flocculus

Large areas of lateral hemispheres connected toflocculus connected to cerebral cortex


Cerebellar somatotopy


Cerebellar damageg

• Hypermetria (overshoot) : finger-to-noseyp ( ) g• Intention tremor : during action

At i l f di ti d kill• Ataxia : loss of coordination, and skill

• Nystagmus, balance , gait, speech

• Cerebellar affective disorder : executive,Cerebellar affective disorder : executive, emotional, personality (children)


E i di b ll t iEpisodic cerebellar ataxia

Rare condition butRare condition, but symptoms typical of cerebellar damage


Cerebellar inactivation


Cerebellar t l lcortex molecular

granularPurkinjeg a u a

climbingclimbing fibres

mossy fibres


Parallel fibresCerebellar cortexPurkinje cellsGolgi cells

Mossy fibresCli bi fibClimbing fibres


Cerebellar circuits – well documented and simple 1-layer system


GolgiCerebellar cortical connections

stellate & basket

parallel fibres & granule cells

connections

PurkinjePurkinjebasket

mossy climbing fibre (from i f li )

fibres (pons)

to cerebellar

nuclei

Oct-10 RCM - BMedSci Neuro III 18 of 36inf. olive)

Cell numbers (very approx.)( y pp )

• Total: 105,000,000,000• Granule cells 101,000,000,000• Purkinje cells 15-30 million• Golgi, basket, stellate 150-200 million• Nuclear cells 5 million

P ki j ll i t• Purkinje cell inputs:from Parallel fibres 200,000from Climbing fibres 1from Climbing fibres 1


Fractured somatotopy


Topographical output


Saggital in-out organizationgg g


Climbing fibre induced

+LTD

Purkinjecell

Inhibitoryinterneurons

- +

Cerebellar l i

+-

climbing fibres nuclei

+thalamus mainly to motor

& premotor cortex

red nucleus to inferior t ti l

inputsoutputs

red nucleus to inferior olive sensory-motor cortical

areas, parietal cortex, spinal cord


Cerebellar learninggVOR gain:• head velocity via mossy fibres error signal viahead velocity via mossy fibres, error signal via

climbing fibres• LTD reduces P-cell inhibition of nuclei, disinhibition of

direct pathwaydirect pathway• “push-pull” mechanism in bilateral cerebellum• Combines to fine tune direct pathway gainCo b es to e tu e d ect pat ay ga• Fast pathway – 14 ms latencyEye-blink:Eye blink: • CS via mossy fibres; US via climbing fibres• LTD selects out specific inputs, disinhibits nuclear

llcells• Important role in timing of CR• Slow: controls blink at ~500 ms after CSOct-10 RCM - BMedSci Neuro III 24 of 36

Slow: controls blink at 500 ms after CS

Complex LTD induction (!!)p ( )Parallel fibres: excitation

f P ki j llof Purkinje cell Climbing fibres: gstrong excitation leads to opening of VGCCsCa++ combined with mGluR activation triggers protein kinase Cprotein kinase CPhosphorylation of AMPA receptors LTDreceptors …LTD


LTD and learning of VOR gaing g

Input : vestibular

P ki j I hibit

+- +

Input : vestibular signal of head motionOutput : Purkinje

cellInhibitory

interneurons

-

+Output : modulation of direct path to ocular motor

Vestibular nucleus

+neurons

Semi-circ

+Training signal :retinal slip signal on Semi circ.

canalsOMNsp g

climbing fibres


parallel fibres & granule cellsVOR gain

PurkinjeParallel fibre-Purkinje cell j

LTD

CF: retinalslip (H-E) MF: vestibular

head velocityLTD –modulated

+head velocity

+

modulated inhibition -

Lateral vestibular nuclei

ocular motor

ne rons

“push-pull” from bilateral circuits


neurons

Simple/complex spike codes


Complex spike event detection


parallel fibres & granule cellsEye blink CC

PurkinjeLTD driven selection of

inputs

CS : tone, light, touch etc

+

US :

touch etc

air puffPremotor neurons

Eyelid motor

neurons


neurons

Skill learning


Visuo-motor recalibration• Prism glasses distort visual inputs – need to adjust

movement output to recalibratep• Short term learning• Blocked by cerebellar lesiony

(Martin et al, 1996)


Eye-hand coordination


CEREBRAL FRONTAL LOBE

Cerebello-cerebral processing

PRE-FRONTALCORTEX

MOTOR CORTEX

MANIPULATION OF MANIPULATION OFMANIPULATION OFINFORMATION

MANIPULATION OFMUSCLES

CEREBELLAR DENTATE NUCLEUS

VENTRAL DORSAL PARTVENTRAL DORSAL PART


Cerebellar-cerebral processingp g

CEREBRAL FRONTAL LOBE

PRE-FRONTAL MOTOR CORTEXPRE FRONTALCORTEX

MOTOR CORTEX

MANIPULATION OFINFORMATION

MANIPULATION OFMUSCLESINFORMATION MUSCLES

CEREBELLAR DENTATE NUCLEUS

VENTRAL DORSAL PART


Summaryy• Cerebellar cortex: big and (relatively!) simple• Important for all skilful movement• Huge numbers of parallel fibres bringingHuge numbers of parallel fibres bringing

diverse sensory-motor input to Purkinje cells• Climbing fibres induce parallel fibre : P cell• Climbing fibres induce parallel fibre : P-cell

LTD – the main (but not only) mechanismAdj t VOR i t l i l• Adjusts VOR gain, supports classical conditioning of eye-blink (& other reflexes)

• Predictive control


cerebellum: “little brain” cerebellum

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