Neural Plasticity: Long-term Depression

Neural Plasticity:Long-term Depression Lesson 16

Long-term Depression • Hippocampus • Low frequency stimulation • 1 Hz over 10-15 min • NMDA & Ca2+ -dependent • Low Ca2+  phosphatase activity • Cerebellum • mGlu1-R • Different mechanism ~

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

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 ~

Spinocerebellum Cerebrocerebellum Vestibulocerebellum I n t e r p o s e d F a s t i g i a l Dentate

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

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

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 • 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 • from spinal cord & brainstem nuclei • climbing fibers • cerebral cortex & spinal cord • via inferior olivary nucleus ~

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 ~

Cerebellum: 3 layered cortex Molecular Purkinje Granule Mossy fibers Climbing 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 fiberinfluence • input specificity • only affects active synapses of a parallel fiber ~

LTD Mechanisms • 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 ~

LTD Mechanisms • mGluR1 • metabotropic • cGMP-mediated • intracellular Ca++ stores • activation of phosphatases • Knockout mice • lack mGluR1 • loss of motor coordination ~

Neural Plasticity: Long-term Depression