Neural Plasticity Lecture 7

Neural Plasticity n Nervous System is malleable l learning occurs n Structural changes l increased dendritic branching l new synapses n Changes in synaptic efficiency l Long-term potentiation l Long-term depression ~

Neural Mechanism of Memory n Donald Hebb n Short-term Memory l Change in neural activity l not structural l temporary n Reverberatory Circuits - l cortical loops of activity ~

Reverberating Loops n Maintains neural activity for a period l Activity decays ~

Hebb’s Postulate n Long-Term Memory l required structural change in brain l relatively permanent n Hebb Synapse l use strengthens synaptic efficiency l concurrent activity required pre- & postsynaptic neurons ~

Long-term Potentiation n According to Hebb rule l use strengthens synaptic connection n Synaptic facilitation l Structural changes l Simultaneous activity n Experimentally produced l hippocampal slices l associative learning also ~

Inducing LTP Stimulating electrode Record DG Perforant Pathway

-70mv - + Postsynaptic Potential Single elec. stimulation 100 stim. burst Single stim.

n Strong, high frequency stimulation n Minimum stimulation l 1 + burst of 4 l 4-7 Hz Theta l HC: Arousal & REM ~ Pattern Of Stimulation

LTP Duration n Experimentally-induced LTP n Intact animals l seconds - months n HC slice l 40 hrs ~

LTP: Molecular Mechanisms n Presynaptic & Postsynaptic changes n HC ---> Glutamate l excitatory n 2 postsynaptic receptor subtypes l AMPA ---> Na+ l NMDA ---> Ca++ n Glu ligand for both ~

NMDA Receptor n N-methyl-D-aspartate n Glu binding opens channel? l required, but not sufficient n Membrane must be depolarized l before Glu binds ~

Single Action Potential n Glu ---> AMPA l depolarization n Glu ---> NMDA l does not open l Mg++ blocks channel l no Ca++ into postsynaptic cell n Followed by more APs ~

NMDA Mg G Ca++ G AMPA Na+

NMDA G Ca++ G Mg AMPA Na+

Activation of NMDA-R n Ca++ channel l chemically-gated l voltage-gated Mg++ blocks channel n Ca++ influx --->post-synaptic changes l strengthens synapse ~

LTP: Postsynaptic Changes n Receptor synthesis n More synapses n Shape of dendritic spines n Nitric Oxide synthesis ~

Presynaptic Axon Terminal Dendritic Spine Before LTP

Presynaptic Axon Terminal Dendritic Spine After LTP less Fodrin Less resistance

Nitric Oxide - NO n Retrograde messenger l Hi conc. ---> poisonous gas n Hi lipid solubility l storage? n Synthesis on demand l Ca++ ---> NO synthase ---> NO n Increases NT synthesis in presynaptic neuron l more released during AP ~

G Ca++ G NOSNO cGMP Glu

Cerebellum n Motor functions l Coordination of movements l Regulation of posture n Indirect control l Adjust outputs of descending tracts n Also nonmotor functions l memory/language ~ The Cerebellum & Long-term Depression

Cerebellum: Anatomy n Folia & lobules l analogous to sulci & gyri n Vermis - along midline l output ---> ventromedial pathway n Hemispheres l output ---> lateral pathway n Deep cerebellar nuclei l fastigial, interposed, & dentate l Major output structures ~

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

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

Cerebellum: 3 layered cortex n Molecular layer l parallel fibers l axons of granule cells runs parallel to long axis of folium n Purkinge cell layer l large somas l axons to underlying white matter perpendicular to main axis of folium ~

Cerebellum: 3 layered cortex n Purkinge cell layer l large somas l axons to underlying white matter l perpendicular to main axis of folium ~

Cerebellum: 3 layered cortex n Granular layer innermost layer l small, densely packed granule cells l > # neurons in cerebral cortex ~

Cerebellum: 3 layered cortex Molecular Purkinje Granule

Cerebellum: & Motor Learning n Purkinje cells only output from cerebellar cortex l inhibit deep cerebellar nuclei n Input to Purkinje cells l Mossy fibers via parallel fibers from spinal cord & brainstem nuclei l climbing fibers cerebral cortex & spinal cord via inferior olivary nucleus ~

Cerebellum: & Motor Learning n 1 Purkinje cell synapses.. l 1 each with 200,000 parallel fibers l 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 n Long-term depression (LTD) l requires concurrent activity l climbing & parallel fibers active together  in activity of specific Purkinje cells n Climbing fibers may carry error signals corrections --->  parallel fiber  influence n input specificity l only affects active synapses of a parallel fiber ~

LTD Mechanisms n Similar to LTP l * changes are postsynaptic l Glutamate receptors

LTD Mechanisms n *Requires concurrent activity n Climbing fiber 1. Ca++ *influx - voltage-gated n Parallel fibers activate 2. AMPA - Na+ influx 3. mGLUR1 n AMPA desensitized l  Na+ influx ~

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