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 neuron
pre
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