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synaptic plasticity
Basic Neuroscience NBL 120
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classical conditioning
CS (neutral)- no response
US- UR
After pairing:CS- CR
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ability to learn the relationship between different stimuli / events so that we can make reasonable predictions if we are faced with a certain situation
learning & memory => goodaddiction => bad
associative learning
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learning & memory in taxi drivers
PET study during recall of London route
(Maguire et al, 1997)
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place cells
some pyramidal cells in the hippocampus have preferred spatial orientations fire in bursts
(O’Keefe & Dostrovsky, 1971)
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muscle
motor neuron
pre
post
control
muscle
motor neuron
nmj
how is a synapse plastic?
synapses “remember” previous activity short-term, e.g. post-tetanic potentiation at the nmj
time
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Hebbian learning
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 ”
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Johnson & Wu (1995)
hippocampal “integrated circuit”
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in reality…..
before after
ampl
itude
time (hrs)
first demonstration of LTP
high-frequency train
rapid induction lasts weeks in vivo
Bliss & Lomo (1973)
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properties of LTP
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cellular mechanisms underlying LTP
inductionmaintenance
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excitatory synaptic transmission
NMDA vs non-NMDA synaptic transmission
AP5
AP5
control
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LTP depends specifically on NMDA receptor activation
AP5 prevents high frequency-induced LTP
(Collingridge et al, 1983)
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what is special about NMDA receptors?voltage-gated channels: voltageligand-gated channels: transmitterNMDA receptors: both
+ - +
+++
- - -
out
in
Mg+
Mg+
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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:
specificity associativity / co-operativity spatial/temporal requirements
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how does the NMDA receptor cause a change in synaptic strength?
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synaptic transmission is unreliable
increased transmitter releasealtered or new receptorsnew synapses
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NMDA receptors, hippocampus and LTP learning and memory
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NMDA receptor-dependent learning
spatial memory task visual task
“Morris” water maze
Morris et al (1990)
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LTP and learning
saturation of LTP prevents learning a new spatial task
new learning can occur after LTP decay
LTP decay
Castro et al (1989)
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a natural LTP? animals raised in a complex environment show
enhanced synaptic responses in the hippocampus
Sharp et al (1985)
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hippocampus= temporary memory storage
new patterns stored rapidly and transientlygradual transfer to neocortexlong-term storage with reduced interference
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diffuse storage in cortex?
computational theoriesMarr (1970’s)sensory input to neocortex
stored by association repetition - association partial pattern recall
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compulsive use / abuse of a drug despite adverse consequences
addiction - definition
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recollections of an addict:recollections of an addict:
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Skinner-boxlever-press > rewardrate reward
electrical self-stimulation
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“a hungry animal often ignored available food in favor of the pleasure of stimulating itself electrically .... 2000 times per hour for 24 consecutive hours”
(Olds 1956)
“pleasure centers”
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where are the pleasure centers?
medial forebrain bundle VTA - Nucleus Accumbens (after Koob 1992)
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dopamine
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DA neurons and reward
(Schultz et al, 1993)
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drug abuse is a form of associative learning
associated cues could trigger “craving” nicotine is continuously
paired with taste and smell of cigarettes
heroin or other drug use may be associated with a specific setting
evidence………….
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VTA DA response becomes associated with the sound cue i.e. DA response predicts reward
learning
predicting reward
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displacement of [11C]raclopride binding by DA release
“craving”PET scan
(Volkow et al, 1997)
MP = methylphenidate “RITALIN”
what happens to DA in addicts?
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associations - summary
synaptic plasticity hippocampus / cortex NMDA receptor - coincidence detector Mg2+ & Ca2+
addiction midbrain - VTA / Nucleus Accumbens Dopamine predictive cues
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(from McNaughton & Morris, 1987)
in theory…..