Transcript BN16 Neural plasticity

Neural Plasticity:
Long-term
Depression
Lesson 16
Long-term Depression
Hippocampus
 Low frequency stimulation
 1 Hz over 10-15 min
2+ -dependent
 NMDA & Ca
2+   phosphatase activity
 Low Ca
 Cerebellum
 mGlu1-R
 Different mechanism ~
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Cerebellum
Motor functions
 Coordination of movements
 Regulation of posture
 Indirect control
 Adjust outputs of descending tracts
 Also nonmotor functions
 memory/language ~
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Cerebellum: Anatomy
Folia & lobules
 analogous gyri & lobes
 Vermis - along midline
 output  ventromedial pathway
 Hemispheres
 output  lateral pathway
 Deep cerebellar nuclei
 fastigial, interposed, & dentate
 Major output structures ~
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Spinocerebellum
Cerebrocerebellum
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Vestibulocerebellum
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Dentate
Cerebellum
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Programs ballistic movements
 feed-forward control
no feedback during execution
direction, force, & timing
 long term modification of circuits
 Motor learning
 shift from conscious  unconscious ~
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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: 3 layered cortex
1. Molecular layer

parallel fibers

axons of granule cells
runs parallel to long axis of folium ~
Cerebellum: 3 layered cortex
2. Purkinge cell layer
 large somas
 axons to underlying
white matter
perpendicular to main
axis of folium ~
Cerebellum: 3 layered cortex
3. Granular layer
• innermost layer
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small, densely packed granule cells
> # neurons in cerebral cortex ~
Cerebellum: 3 layered cortex
Molecular
Purkinje
Granule
Cerebellum: & Motor Learning
Purkinje cells only output from cerebellar
cortex
 inhibit deep cerebellar nuclei
 Input to Purkinje cells
 Mossy fibers via parallel fibers
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• from spinal cord & brainstem nuclei

climbing fibers
• cerebral cortex & spinal cord
• via inferior olivary nucleus ~
Cerebellum: & Motor Learning
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1 Purkinje cell synapses..
 1 each with 200,000 parallel fibers
 Many with 1 climbing fiber
• strong synaptic connections
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Climbing fibers effects of mossy fibers
transient ~
Cerebellum: 3 layered cortex
Molecular
Purkinje
Granule
Climbing fibers
Mossy fibers
Cerebellum: & Motor Learning
Long-term depression (LTD)
 requires concurrent activity
 climbing & parallel fibers active together
  in activity of specific Purkinje cells
 Climbing fibers may carry error signals
 corrections  parallel fiber influence
 input specificity
 only affects active synapses of a parallel
fiber ~
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LTD Mechanisms
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Similar to LTP
 changes are postsynaptic
 Glutamate receptors ~
LTD Mechanisms
Requires concurrent activity
 Climbing fiber
1. Ca++ influx - voltage-gated
 Parallel fibers activate
2. AMPA - Na+ influx
3. mGLUR1
 AMPA desensitized
  Na+ influx ~
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LTD Mechanisms
mGluR1
 metabotropic
 cGMP-mediated
 intracellular Ca++ stores
 activation of phosphatases
 Knockout mice
 lack mGluR1
 loss of motor coordination ~
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