~BN15 Neural plasticity - LTP.ppt

Neural Plasticity:Long-term

Potentiation

Lecture 15

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 ~

Before LTP

After LTP

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-amino-3-hydroxyl-5-methyl-4-

isoxazole-propionate depolarization

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

Followed by more APs ~

NMDAMg

G

Ca++

GAMPA

Na+

G

NMDA

MgG G

Ca++

AMPA

Na+G

NMDAG

Ca++

G

Mg

AMPA

Na+

G

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

G