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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)
Oct-10 RCM - BMedSci Neuro III 3 of 36
Cerebellum: “little brain”
Oct-10 RCM - BMedSci Neuro III 4 of 36
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
Oct-10 RCM - BMedSci Neuro III 5 of 36
Heavy cortical folding in transverse plane:10 lobes
Deep cerebellar nuclei
Oct-10 RCM - BMedSci Neuro III 6 of 36
Cortical nomenclature
Deep cerebellar nucleiLateral (or dentate)Interposed (interpositus)Interposed (interpositus)
emboliformglobose
Medial (fastigial)
Oct-10 RCM - BMedSci Neuro III 7 of 36
( 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
Oct-10 RCM - BMedSci Neuro III 8 of 36
Thin cortical sheetPurkinje
cellscells
1 mm1 mm
Section though bird b ll tcerebellar cortex
Cajal 1905
Oct-10 RCM - BMedSci Neuro III 9 of 36
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
Oct-10 RCM - BMedSci Neuro III 10 of 36
Cerebellar somatotopy
Oct-10 RCM - BMedSci Neuro III 11 of 36
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)
Oct-10 RCM - BMedSci Neuro III 12 of 36
E i di b ll t iEpisodic cerebellar ataxia
Rare condition butRare condition, but symptoms typical of cerebellar damage
Oct-10 RCM - BMedSci Neuro III 13 of 36
Cerebellar inactivation
Oct-10 RCM - BMedSci Neuro III 14 of 36
Cerebellar t l lcortex molecular
granularPurkinjeg a u a
climbingclimbing fibres
mossy fibres
Oct-10 RCM - BMedSci Neuro III 15 of 36
Parallel fibresCerebellar cortexPurkinje cellsGolgi cells
Mossy fibresCli bi fibClimbing fibres
Oct-10 RCM - BMedSci Neuro III 16 of 36
Cerebellar circuits – well documented and simple 1-layer system
Oct-10 RCM - BMedSci Neuro III 17 of 36
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
Oct-10 RCM - BMedSci Neuro III 19 of 36
Fractured somatotopy
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Topographical output
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Saggital in-out organizationgg g
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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
Oct-10 RCM - BMedSci Neuro III 23 of 36
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
Oct-10 RCM - BMedSci Neuro III 25 of 36
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
Oct-10 RCM - BMedSci Neuro III 26 of 36
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
Oct-10 RCM - BMedSci Neuro III 27 of 36
neurons
Simple/complex spike codes
Oct-10 RCM - BMedSci Neuro III 28 of 36
Complex spike event detection
Oct-10 RCM - BMedSci Neuro III 29 of 36
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
Oct-10 RCM - BMedSci Neuro III 30 of 36
neurons
Skill learning
Oct-10 RCM - BMedSci Neuro III 31 of 36
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)
Oct-10 RCM - BMedSci Neuro III 32 of 36
Eye-hand coordination
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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
Oct-10 RCM - BMedSci Neuro III 34 of 36
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
Oct-10 RCM - BMedSci Neuro III 35 of 36
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
Oct-10 RCM - BMedSci Neuro III 36 of 36