Neural Plasticity

Lecture 7

Neural Plasticity

Nervous System is malleable learning occurs

Structural changes increased dendritic branching new synapses

Changes in synaptic efficiency Long-term potentiation Long-term depression ~

Neural Mechanism of Memory

Donald Hebb Short-term Memory

Change in neural activity not structural temporary

Reverberatory Circuits - cortical loops of activity ~

Reverberating Loops

Maintains neural activity for a period Activity decays ~

Hebb’s Postulate

Long-Term Memory required structural change in brain relatively permanent

Hebb Synapse use strengthens synaptic efficiency concurrent activity required

• pre- & postsynaptic neurons ~

Long-term Potentiation

According to Hebb rule use strengthens synaptic connection

Synaptic facilitation Structural changes Simultaneous activity

Experimentally produced hippocampal slices associative learning also ~

Inducing LTP

Stimulating electrode

Record

DGPerforantPathway

-70mv

-

+

Postsynaptic Potential

Single elec. stimulation

100 stim. burst

Single stim.

Strong, high frequency stimulation Minimum stimulation

1 + burst of 4 4-7 Hz

• Theta HC: Arousal & REM ~

Pattern Of Stimulation

LTP Duration

Experimentally-induced LTP Intact animals

seconds - months HC slice

40 hrs ~

LTP: Molecular Mechanisms

Presynaptic & Postsynaptic changes HC ---> Glutamate

excitatory 2 postsynaptic receptor subtypes

AMPA ---> Na+ NMDA ---> Ca++

Glu ligand for both ~

NMDA Receptor

N-methyl-D-aspartate Glu binding opens channel?

required, but not sufficient Membrane must be depolarized

before Glu binds ~

Single Action Potential

Glu ---> AMPA depolarization

Glu ---> NMDA does not open Mg++ blocks channel no Ca++ into postsynaptic cell

Followed by more APs ~

NMDAMg

G

Ca++

GAMPA

Na+

NMDAG

Ca++

G

Mg

AMPA

Na+

Activation of NMDA-R

Ca++ channel chemically-gated voltage-gated

Mg++ blocks channel Ca++ influx --->post-synaptic changes

strengthens synapse ~

LTP: Postsynaptic Changes

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

PresynapticAxon Terminal

Dendritic Spine

Before LTP

PresynapticAxon Terminal

Dendritic Spine

After LTP

less Fodrin

Less resistance

Nitric Oxide - NO

Retrograde messenger Hi conc. ---> poisonous gas

Hi lipid solubility storage?

Synthesis on demand Ca++ ---> NO synthase ---> NO

Increases NT synthesis in presynaptic neuron more released during AP ~

G Ca++

G

Ca++NOSNO

NO cGMP Glu

Cerebellum Motor functions

Coordination of movements Regulation of posture

Indirect control Adjust outputs of descending tracts

Also nonmotor functions memory/language ~

The Cerebellum & Long-term Depression

Cerebellum: Anatomy

Folia & lobules analogous to sulci & gyri

Vermis - along midline output ---> ventromedial pathway

Hemispheres output ---> lateral pathway

Deep cerebellar nuclei fastigial, interposed, & dentate Major output structures ~

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

Molecular layer parallel fibers axons of granule cells

runs parallel to long axis of folium Purkinge cell layer

large somas axons to underlying white matter

perpendicular to main axis of folium ~

Cerebellum: 3 layered cortex

Purkinge cell layer large somas axons to underlying

white matter perpendicular to

main axis of folium ~

Cerebellum: 3 layered cortex

Granular layerinnermost 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 fibersClimbing 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 ~