synaptic plasticity

DENT/OBHS 131Neuroscience

2009

Learning objectives

1. Understand the properties of long-term potentiation (LTP) that define it as a model of experience-dependent synaptic plasticity

2. Discuss the characteristics that make NMDA receptors coincident detectors cable of initiating associative information storage (Pavlov’s dog)

3. Describe the relationship between NMDA receptors, LTP and behavioral memory

learning & memory in taxi drivers

PET study during recall of London route

(Maguire et al, 1997)

Papez circuit / loop

place cells / maps

some pyramidal cells in the hippocampus (and other parts of Papez circuit) have preferred spatial orientations & place maps

(O’Keefe & Dostrovsky, 1971)

Hebbian learning….in theory

longer term plasticityHebbian learning

Hebb (1949) hypothesized that “ if one neuron frequently takes part in exciting another, some growth process or metabolic change takes place in one or both cells and the strength of their connection increases ”

muscle

motor neuronpre

post

control

muscle

motor neuron

nmj

Synapses are plastic

synapses “remember” previous activity short-term, e.g. post-tetanic potentiation at the nmj

time

Can synaptic plasticity explain learning?

CS (neutral)- no response

US- UR

After pairing:CS- CR

Learning Objective #1

Understand the properties of long-term potentiation (LTP) that define it as a model of experience-dependent synaptic plasticity

Long-term potentiation (LTP)

before after

amplitude

time (hrs)

first demonstration of LTP

high-frequency train

rapid induction lasts weeks in vivo

Bliss & Lomo (1973)

properties of LTP

Learning Objective #2

Discuss the characteristics that make NMDA receptors coincident detectors cable of initiating associative information storage (Pavlov’s dog)

cellular mechanisms underlying LTP

inductionmaintenance

AP5

AP5

control

excitatory synaptic transmission

NMDA vs non-NMDA synaptic transmission

LTP depends specifically on NMDA receptor activation

AP5 prevents high frequency-induced LTP

(Collingridge et al, 1983)

what is special about NMDA receptors?voltage-gated channels: voltageligand-gated channels: transmitterNMDA receptors: both

+ - +

+++

- - -

out

in

Mg+

Mg+

NMDA receptor: a molecular switch

co-incidence detector requires both presynaptic

activity (glutamate) and postsynaptic depolarization (relieve Mg block) satisfies Hebbian co-incidence rules explains LTP properties:

how does the NMDA receptor cause a change in synaptic strength?

synaptic transmission is unreliable

increased transmitter releasealtered or new receptorsnew synapses

Johnson & Wu (1995)

hippocampal “integrated circuit”

associative pattern storage

from McNaughton & Morris (1987)

Learning Objective #3

Describe the relationship between NMDA receptors, LTP and behavioral memory

spatial memory task visual task

“Morris” water maze

Morris et al (1990)

NMDA receptor-dependent learning

LTP decay

Castro et al (1989)

LTP and learning

saturation of LTP prevents learning a new spatial task

new learning can occur after LTP decay

diffuse storage in cortex?

computational theories e.g., Marr (1970’s)

sensory input to neocortex stored by association repetition - association partial pattern recall