Neural Plasticity Lecture 7 Neural Plasticity Nervous System

Neural Plasticity Lecture 7

Neural Plasticity 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 ~ n

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

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

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

Long-term Potentiation 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 ~ n

Inducing LTP Stimulating electrode Perforant Pathway Record DG

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

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

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

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

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

Single Action Potential 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 ~ n

Ca++ Na+ AMPA G G Mg NMDA

Mg Na+ AMPA G Ca++ G NMDA

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 Receptor synthesis n More synapses n Shape of dendritic spines n Nitric Oxide synthesis ~ n

Before LTP Presynaptic Axon Terminal Dendritic Spine

After LTP Presynaptic Axon Terminal less Fodrin Less resistance Dendritic Spine

Nitric Oxide - NO 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 ~ n

NO c. GMP Glu Ca++ G NO NOS G Ca++

The Cerebellum & Long-term Depression Cerebellum 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 ~ n

Cerebellum: Anatomy 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 ~ n

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

Cerebellum 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 ~ n

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 l 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 l inhibit deep cerebellar nuclei n Input to Purkinje cells l Mossy fibers via parallel fibers n 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 n 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) l requires concurrent activity l climbing & parallel fibers active together l in activity of specific Purkinje cells n Climbing fibers may carry error signals l corrections ---> parallel fiber influence n input specificity l only affects active synapses of a parallel fiber ~ n

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

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

LTD Mechanisms m. Glu. R 1 l metabotropic l c. GMP-mediated l intracellular Ca++ stores l activation of phosphatases n Knockout mice l lack m. Glu. R 1 l loss of motor coordination ~ n