Synaptic Plasticity in Neural Networks Needs Homeostasis ...
synaptic plasticity
description
Transcript of synaptic plasticity
synaptic plasticityBasic Neuroscience NBL 120
classical conditioning
CS (neutral)- no response
US- UR
After pairing:CS- CR
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
learning & memory in taxi drivers
PET study during recall of London route
(Maguire et al, 1997)
place cells
some pyramidal cells in the hippocampus have preferred spatial orientations fire in bursts
(O’Keefe & Dostrovsky, 1971)
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
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 ”
Johnson & Wu (1995)
hippocampal “integrated circuit”
in reality…..
before after
ampl
itude
time (hrs)
first demonstration of LTP
high-frequency train
rapid induction lasts weeks in vivo
Bliss & Lomo (1973)
properties of LTP
cellular mechanisms underlying LTP
inductionmaintenance
excitatory synaptic transmission NMDA vs non-NMDA synaptic transmission
AP5
AP5
control
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:
specificity associativity / co-operativity spatial/temporal requirements
how does the NMDA receptor cause a change in synaptic strength?
synaptic transmission is unreliable
increased transmitter releasealtered or new receptorsnew synapses
NMDA receptors, hippocampus and LTP learning and memory
NMDA receptor-dependent learningspatial memory task visual task
“Morris” water maze
Morris et al (1990)
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)
a natural LTP? animals raised in a complex environment show
enhanced synaptic responses in the hippocampus
Sharp et al (1985)
hippocampus= temporary memory storage
new patterns stored rapidly and transientlygradual transfer to neocortexlong-term storage with reduced interference
diffuse storage in cortex?
computational theoriesMarr (1970’s)sensory input to neocortex
stored by association repetition - association partial pattern recall
compulsive use / abuse of a drug despite adverse consequences
addiction - definition
recollections of an addict:recollections of an addict:
Skinner-boxlever-press > rewardrate reward
electrical self-stimulation
“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”
where are the pleasure centers?
medial forebrain bundle VTA - Nucleus Accumbens (after Koob 1992)
dopamine
DA neurons and reward
(Schultz et al, 1993)
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………….
VTA DA response becomes associated with the sound cue i.e. DA response predicts reward
learning
predicting reward
displacement of [11C]raclopride binding by DA release
“craving”PET scan
(Volkow et al, 1997)
MP = methylphenidate “RITALIN”
what happens to DA in addicts?
associations - summary
synaptic plasticity hippocampus / cortex NMDA receptor - coincidence detector Mg2+ & Ca2+
addiction midbrain - VTA / Nucleus Accumbens Dopamine predictive cues
(from McNaughton & Morris, 1987)
in theory…..