~BN16 Neural plasticity - LTD.ppt

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~BN16 Neural plasticity - LTD.ppt

  1. 1. Neural Plasticity: Long-term Depression Lecture 16
  2. 2. Cerebellum <ul><li>Motor functions </li></ul><ul><ul><li>Coordination of movements </li></ul></ul><ul><ul><li>Regulation of posture </li></ul></ul><ul><li>Indirect control </li></ul><ul><ul><li>Adjust outputs of descending tracts </li></ul></ul><ul><li>Also nonmotor functions </li></ul><ul><ul><li>memory/language ~ </li></ul></ul>
  3. 3. Cerebellum: Anatomy <ul><li>Folia & lobules </li></ul><ul><ul><li>analogous gyri & lobes </li></ul></ul><ul><li>Vermis - along midline </li></ul><ul><ul><li>output  ventromedial pathway </li></ul></ul><ul><li>Hemispheres </li></ul><ul><ul><li>output  lateral pathway </li></ul></ul><ul><li>Deep cerebellar nuclei </li></ul><ul><ul><li>fastigial, interposed, & dentate </li></ul></ul><ul><ul><li>Major output structures ~ </li></ul></ul>
  4. 5. F a s t i g i a l I n t e r p o s e d Dentate Spinocerebellum Cerebrocerebellum Vestibulocerebellum
  5. 6. Cerebellum <ul><li>Programs ballistic movements </li></ul><ul><ul><li>feed-forward control </li></ul></ul><ul><ul><ul><li>no feedback during execution </li></ul></ul></ul><ul><ul><li>direction, force, & timing </li></ul></ul><ul><ul><li>long term modification of circuits </li></ul></ul><ul><li>Motor learning </li></ul><ul><ul><li>shift from conscious  unconscious ~ </li></ul></ul>
  6. 7. Cerebellum <ul><li>Acts as comparator for movements </li></ul><ul><ul><li>compares intended to actual performance </li></ul></ul><ul><li>Correction of ongoing movements </li></ul><ul><ul><li>internal & external feedback </li></ul></ul><ul><ul><li>deviations from intended movement ~ </li></ul></ul>
  7. 8. Cerebellum: 3 layered cortex <ul><li>1. Molecular layer </li></ul><ul><ul><li>parallel fibers </li></ul></ul><ul><ul><li>axons of granule cells </li></ul></ul><ul><ul><ul><li>runs parallel to long axis of folium ~ </li></ul></ul></ul>
  8. 9. Cerebellum: 3 layered cortex <ul><li>2. Purkinge cell layer </li></ul><ul><ul><li>large somas </li></ul></ul><ul><ul><li>axons to underlying white matter </li></ul></ul><ul><ul><ul><li>perpendicular to main axis of folium ~ </li></ul></ul></ul>
  9. 10. Cerebellum: 3 layered cortex <ul><li>3. Granular layer </li></ul><ul><ul><ul><li>innermost layer </li></ul></ul></ul><ul><ul><li>small, densely packed granule cells </li></ul></ul><ul><ul><li>> # neurons in cerebral cortex ~ </li></ul></ul>
  10. 11. Cerebellum: 3 layered cortex Molecular Purkinje Granule
  11. 12. Cerebellum: & Motor Learning <ul><li>Purkinje cells only output from cerebellar cortex </li></ul><ul><ul><li>inhibit deep cerebellar nuclei </li></ul></ul><ul><li>Input to Purkinje cells </li></ul><ul><ul><li>Mossy fibers via parallel fibers </li></ul></ul><ul><ul><ul><li>from spinal cord & brainstem nuclei </li></ul></ul></ul><ul><ul><li>climbing fibers </li></ul></ul><ul><ul><ul><li>cerebral cortex & spinal cord </li></ul></ul></ul><ul><ul><ul><li>via inferior olivary nucleus ~ </li></ul></ul></ul>
  12. 13. Cerebellum: & Motor Learning <ul><li>1 Purkinje cell synapses.. </li></ul><ul><ul><li>1 each with 200,000 parallel fibers </li></ul></ul><ul><ul><li>Many with 1 climbing fiber </li></ul></ul><ul><ul><ul><li>strong synaptic connections </li></ul></ul></ul><ul><li>Climbing fibers   effects of mossy fibers </li></ul><ul><ul><ul><li>transient ~ </li></ul></ul></ul>
  13. 14. Cerebellum: 3 layered cortex Molecular Purkinje Granule Mossy fibers Climbing fibers
  14. 15. Cerebellum: & Motor Learning <ul><li>Long-term depression (LTD) </li></ul><ul><ul><li>requires concurrent activity </li></ul></ul><ul><ul><li>climbing & parallel fibers active together </li></ul></ul><ul><ul><li>  in activity of specific Purkinje cells </li></ul></ul><ul><li>Climbing fibers may carry error signals </li></ul><ul><ul><li>corrections   parallel fiber  influence </li></ul></ul><ul><li>input specificity </li></ul><ul><ul><li>only affects active synapses of a parallel fiber ~ </li></ul></ul>
  15. 16. LTD Mechanisms <ul><li>Similar to LTP </li></ul><ul><ul><li>changes are postsynaptic </li></ul></ul><ul><ul><li>Glutamate receptors ~ </li></ul></ul>
  16. 17. LTD Mechanisms <ul><li>Requires concurrent activity </li></ul><ul><li>Climbing fiber </li></ul><ul><ul><li>1. Ca++ influx - voltage-gated </li></ul></ul><ul><li>Parallel fibers activate </li></ul><ul><ul><li>2. AMPA - Na+ influx </li></ul></ul><ul><ul><li>3. mGLUR1 </li></ul></ul><ul><li>AMPA desensitized </li></ul><ul><ul><li> Na+ influx ~ </li></ul></ul>
  17. 18. LTD Mechanisms <ul><li>mGluR1 </li></ul><ul><ul><li>metabotropic </li></ul></ul><ul><ul><li>cGMP-mediated </li></ul></ul><ul><ul><li>intracellular Ca++ stores </li></ul></ul><ul><ul><li>activation of phosphatases </li></ul></ul><ul><li>Knockout mice </li></ul><ul><ul><li>lack mGluR1 </li></ul></ul><ul><ul><li>loss of motor coordination ~ </li></ul></ul>

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