Subcortical Motor Systems: Cerebellum

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Subcortical Motor SystemsCerebellum Basal
Ganglia

• Lecture 23

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Motor Loops

• Cortex ---gt Subcortex ---gt Cortex ---gt Spinal
  cord
• Cerebellum
• coordination of movement
• Basal Ganglia
• selection initiation of voluntary movements

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Cerebellum

• Also nonmotor functions
• memory/language
• Motor functions
• Coordination of movements
• Regulation of posture
• Indirect control
• Adjust outputs of descending tracts

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Cerebellum

• Acts as comparator for movements
• compares intended to actual performance
• Correction of ongoing movements
• internal external feedback
• deviations from intended movement

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Cerebellum

• Programs ballistic movements
• feed-forward control
• no feedback during execution
• direction, force, timing
• long term modification of circuits
• Motor learning
• shift from conscious ---gt unconscious

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Cerebellum Anatomy

• Folia lobules
• analogous to sulci gyri
• Vermis - along midline
• output ---gt ventromedial pathway
• Hemispheres
• output ---gt lateral pathway
• Deep cerebellar nuclei
• fastigial, interposed, dentate
• Major output structures

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Divisions Spinocerebellum

• Inputs
• spinal cord trigeminal nerve
• Outputs
• Motor execution
• From fastigial nuclei
• to medial descending tracts
• From interposed nuclei
• to lateral descending tracts

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Divisions Cerebrocerebellum

• Inputs
• from Cortex pons
• Outputs
• Motor planning
• from dentate nuclei
• to motor premotor cortices

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Divisions Vestibulocerebellum

• Inputs
• vestibular nuclei
• Outputs
• Eye movements body equilibrium
• to vestibular nuclei

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I n t e r p o s e d
F a s t i g i a l
Dentate
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Cerebellum 3 layered cortex

• Molecular layer
• parallel fibers
• axons of granule cells
• runs parallel to long axis of folium
• Purkinge cell layer
• large somas
• axons to underlying white matter
• perpendicular to main axis of folium

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Cerebellum 3 layered cortex

• Granular layer
• innermost layer
• small, densely packed granule cells
• gt neurons in cerebral cortex

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Cerebellum 3 layered cortex
Molecular
Purkinje
Granule
Mossy fibers
Climbing fibers
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Cerebellum Motor Learning

• Purkinje cells only output from cerebellar cortex
• inhibit deep cerebellar nuclei
• Input to Purkinje cells
• Mossy fibers via parallel fibers
• from spinal cord brainstem nuclei
• climbing fibers
• cerebral cortex spinal cord
• via inferior olivary nucleus

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Cerebellum Motor Learning

• 1 Purkinje cell synapses..
• 1 each with 200,000 parallel fibers
• Many with 1 climbing fiber
• strong synaptic connections
• Climbing fibers effects of mossy fibers
• transient

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Cerebellum Motor Learning

• Long-term depression
• climbing parallel fibers active together
• in activity of specific Purkinje cells
• Climbing fibers may carry error signals
• corrections ---gt parallel fiber influence
• input specificity
• only affects active synapses of a parallel fiber

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Motor Loop Through Cerebellum

• Lateral cerebellum
• simplest circuit
• 20 million axons
• Cortex ---gt pons cerebellum
• Prefrontal, Motor, PPC
• Pons Cerebellum ---gt thalamus
• VLc - ventrolateral nucleus
• VLc ---gt M1 ---gt lateral pathway

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Lateral Cerebellar Motor Loop
Pons, Cerebellum
VLc
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Cerebellum Damage

• Lesions ---gt no paralysis
• loss of motor coordination
• Dysynergia
• no simultaneous movement of joints
• serial movement only
• Dysmetric movements
• to wrong coordinates
• Alcohol intoxiction
• depression of cerebellar circuits

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Basal Ganglia

• Many nonmotor functions
• memory other cognitive functions
• Indirect control of movement
• Selection Initiation of willed movement
• funnel cortical activation to SMA
• inhibition of inappropriate movement

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Basal Ganglia

• Primary outputs
• prefrontal, M1, M2
• no direct outputs to spinal cord
• Primary inputs
• diverse regions of cortex
• no direct input from sensory receptors

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Basal Ganglia

• Caudate nucleus
  Putamen
• Globus Pallidus

• Substantia Nigra
• tegmentum
• Subthalamic nucleus
• Control slow movements

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Striatum
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Cross section of Tegmentum
Substantia Nigra
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Basal Ganglia Motor Loop
Basal Ganglia
VLo
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Parkinsons Disease

• 1 of population
• Nigrostriatal pathway
• Substantia nigra neurons die
• Progressive loss
• Hypokinesia
• Rigidity
• Bradykinesia
• Akinesia

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SMA

Cortex

Motor Loop
Putamen
VLo
Substantia Nigra
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SMA

Cortex

Parkinsons Disease
Putamen
VLo
X
-
Substantia Nigra
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Parkinsons Disease Treatment

• Basal Ganglia - Cholinergic
• Substantia Nigra - Dopaminergic
• Drug Therapy
• L-DOPA
• Pallidectomy
• Electrical stimulation of Globus pallidus
• Tissue transplants

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Huntingtons Disease (Chorea)

• Rare
• onset 30-40s
• early as 20s
• Degeneration of Striatum
• Caudate
• Putamen
• GABA ACh neurons

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Symptoms

• Khoros dance
• Uncontrollable, jerky movements
• dementia
• Progressive
• eventually fatal

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SMA
Putamen
Huntingtons Disease
X
-
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Huntingtons Disease Cause

• Genetic disorder
• Single dominant gene on chromosome 4
• HD mutation -
• unstable trinucleotide repeat - CAG
• of repeats correlated w/ age of onset

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Huntingtons Disease Cause

• HD gene ---gt huntingtin
• 3 forms
• mutated form binds to protein
• involved in energy production
• neuron starves
• Excitotoxicity contributes to degeneration
• glutamate ---gt Nitric oxide (NO)
• Potential treatment Inhibit NO synthase
  

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Hyperkinesia

• Excessive movement
• Ballism
• violent, flinging movements
• Lesions in subthalamus
• less inhibition of Vlo
• excitation of SMA

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SMA
Striatum
Hyperkinesia (e.g. ballism)
-
X