Transcript Synaptic Plasticity

synaptic plasticity
Basic Neuroscience NBL 120
classical conditioning
CS (neutral)
- no response
US
- UR
After pairing:
CS
- CR
associative learning
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 => good
addiction => bad
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)
how is a synapse plastic?
synapses “remember” previous activity
 short-term, e.g. post-tetanic potentiation at the nmj
control
motor neuron
motor neuron
pre
musclemuscle
nmj
time
post
Hebbian learning
longer term plasticity
Hebbian 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 ”
hippocampal “integrated circuit”
Johnson & Wu (1995)
in reality…..
after
before
amplitude
 first demonstration
of LTP
 high-frequency
train
 rapid induction
 lasts weeks in vivo
time (hrs)
Bliss & Lomo (1973)
properties of LTP
cellular mechanisms underlying LTP
 induction
 maintenance
excitatory synaptic transmission
 NMDA vs non-NMDA
 synaptic transmission
AP5
control
AP5
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: voltage
ligand-gated channels: transmitter
NMDA receptors: both
Mg+
out
+++
Mg+
---
in
+-+
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 release
altered or new receptors
new synapses
NMDA receptors, hippocampus and LTP
learning and memory
NMDA receptor-dependent learning
spatial memory task
visual task
“Morris” water maze
Morris et al (1990)
LTP and learning
LTP
decay
 saturation of
LTP prevents
learning a new
spatial task
 new learning
can occur after
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 transiently
gradual transfer to neocortex
long-term storage with reduced interference
diffuse storage in cortex?
computational theories
Marr (1970’s)
sensory input to neocortex
stored by association
repetition - association
partial pattern recall
addiction - definition
compulsive use / abuse of a
drug despite adverse
consequences
recollections of an addict:
electrical self-stimulation
Skinner-box
lever-press >
reward
rate  reward
“pleasure centers”
 “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)
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………….
predicting reward
VTA DA
response
becomes
associated with
the sound cue
i.e. DA response
predicts reward
learning
what happens to DA in addicts?
displacement of [11C]raclopride binding by DA release
PET scan
MP = methylphenidate
“RITALIN”
“craving”
(Volkow et al, 1997)
associations - summary
 synaptic plasticity
hippocampus / cortex
NMDA receptor - coincidence detector
Mg2+ & Ca2+
 addiction
midbrain - VTA / Nucleus Accumbens
Dopamine
predictive cues
in theory…..
(from McNaughton & Morris, 1987)