Systems Physiology II 6010

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Systems Physiology II 6010
Lecture 6 Motor system The Cerebellum
Bradley Greger, PhD
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The Cerebellum

• The little brain

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The Cerebellum

• Two hemispheres
• Three lobes
• Anterior
• Posterior
• Floculonodular

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The Cerebellum

• Three layered cortex
• Molecular
• Purkinje
• Granular
• Six cell types
• Purkinje
• Granular
• Half the neurons in the brain
• Crystalline architecture
• Should be simple to figure out

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Cerebellar purkinje cells have both simple and
complex spikes

• Simple spikes high frequency, correlated with
  ipsilateral limb movements in anterior lobe
• Complex spikes low frequency, correlated with
  error feedback

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The Cerebellum

• Deep nuclei
• Dendate
• Emboliform
• Globose
• Fastigial
• Non-human primates
• Interpositus
• Emboliform
• Globose
• Output
• Spinal nuclei
• Thalamus

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The Cerebellum

• Cortical Zones
• Spinocerebellum
• Intermediate Hemisphere
• Lateral Hemisphere

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The Cerebellum

• Spinocerebellum

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The Cerebellum

• Intermediate Cerebellum

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The Cerebellum

• Cerebrocerebellum

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The cerebro-cerebellar system

• Regions of cerebral cortex that give rise to
  corticopontine tract and corticorubral tract
• Regions of cerebellum that give rise to
  dentato-thalamic tract
• Closed loop architecture

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Long-term Depression (of synapses)

• Coincidence of simple spikes and complex spikes
• Decrease efficacy of parallel fiber purkinje
  cell synapses
• NO as neurotransmitter

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Two sensory-motor adaptation paradigms
Target-shift Adaptation
Prism Adaptation
Late
Early
Late
Early
Reaching movements Saccadic eye movements
Reaching movements
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Typical adaptation curves
Prism Adaptation
Target Shift Adaptation
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Short-term and long-term sensory-motor adaptation
Short-term
Long-term
Once acquired persists for years
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The acquired sensory-motor mapping is triggered
by context
Prism glasses that shift in the opposite
direction
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pl-Cerebellar Lesions

• Motor ataxia is the clinical hallmark of
  cerebellar lesions
• pl-cerebellum lesions little or no ataxia
  compared to anterior lobe lesions
• Impair sensory-motor adaptation

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Electrophysiology in the cerebellum
Dorsal view of cerebellar cortex
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Visually guided reach adaptation task
Target Appearance
Movement Start
Target Re-appearance
Screen Touched
Hand Returned
Random initial target location Targets were
shifted in eight directions Variable delay in
target reappearance (50, 75, or 150ms)
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Simple spikes were correlated with ipsi-lateral
and contra-lateral limb reaching
Increasing Firing Rate
Decreasing Firing Rate
Monkey 1
Monkey 2
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Simple spike population data for ipsi and contra
lateral limb reaching

• Contrasts with simple spikes in the anterior lobe
  being correlated only with ispilateral limb
  movement

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Simple spikes correlated with movement parameters
irrespective of limb
All findings in pl-cerebellum were present
irrespective of limb used for movement
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Simple spike firing was different on success
versus failure trials
Touch Location on Screen
Success-failure signal
Not correlated with distance
Touch Location Relative to Target
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Success-failure signal appeared approximately
200ms after screen touch
Receiver operating characteristic (ROC)
analysis Gamma probability that an ideal
observer could discriminate two signals
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Complex spike peaks on target appearance (T1)
De-adaptation
Adaptation
Pre-adaptation
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Complex spike peaks on target reappearance (T2)
Adaptation
De-adaptation
Pre-adaptation
Complex spike firing rate constant throughout
adaptation
Norris, Greger, Hathaway, Thach 2004
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T1 and T2 complex spike peaks time locked to
visual stimuli not reach
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T1 complex spike peak related to target location
on screen
Pre-adaptation Trials
Touch relative to target
Target on screen
Touch on screen
ni number of locations with T1 CS in quadrant i
N total number of location with CS mi
number of locations in quadrant i M total
number of locations
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T2 complex spike peak related to target shift
direction
Adaptation Trials
Touch relative to target
Target on screen
Touch on screen
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Direction tuning of T1 and T2 complex spike peaks
correlated
Retinotopic encoding of off-gaze visual targets
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Complex spikes influence simple spike firing rates

• Adaptation SS and CS

• Pre-adaptation SS and CS

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Cerebro-cerebellar interactions
Cerebral plasticity
Cerebellar plasticity