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Learning & memeory presentation Addiction and plasticity (Plasticity…
Learning & memeory presentation
Addiction and plasticity
Need regulation of AMPA in LTP/D
Different receptors
GluR1&4 regulated by experience
GluR1
PKA increases open channel probability - regulates AMPA trafficking
GluR4
Only needs PKA
CaMKII
essential/causal role in LTP
increases channel conduction GluR1
Synaptic insertion
Influence of drugs
2 general mechanisms
circuit level
infuence activation of glutamate
influence LTP/D generation
Psychomotor stimulants
elevate monoamines
modulates excitability
modulates plasticity
Directly on synapses
transmitter level
for example DA receptor
directly modulate LTP/D
Focus on psychostimulants and DA
Plasticity in addiction related brain regions
VTA
Contains DA and GABA that projects to forebrain
Receives Glut from PFC and tegmentum
Drives DA and GABA
LTP/D
NMDA receptor dependent LTP at excitatory
LTD
at excitatory synapses, only requires rise in calcium and activation of PKA (in other areas this is for LTP)
Psychostimulants
initiation of sensitization
is then transferred to other forebrain regions
LTP like process
Because inclreased AMPA/NMDA ratio
=LTP marker
Correlated with transient behavioral sensitization
Enhanced DA transmission
motivation to seek drugs
Cross sensitization between stress and drugs
increase ofDA activity after discontinuation
NAc
For motivated, goal-directed behavior
Mostly medium spiny GABA neurons
innervated by glut projections
Can innervate DA receptors?
interface between limbic and motor
motivation to action
expression of behavioral sensitization
glutamate transmission necessary for drug-seeking behavior
LTP
by stimulating cortical/hipp. afferents
requires NMDA stimulation
LTD
NMDA dependen type doesn't require mGluR
No DA needed
Psychostimulants
reduction of AMPA in subregion
No changes in NMDA
Similar to LTD?
chronic cocain induces LTD of excitatory synapses in NAc shell
subsensitive to glut after withdrawal
Different responses in different locations
DA receptorstimulation
doesn't interfere with LTP but with consequences of stimulation
Normal role may be minimizing single action potential
May need activation from different regions to produce signal
amphetamine may disrupt this
loses dampening effect of DA
single input can induce LTP
Dorsal striatum
inititation, production, sequencing of behavoir
habit-based learning
may drive compulsive behavoir
GABA medium spiny neuron
receive input from glut fibers (cortex, thalamus) and DA fibers (SNc)
Project to GPi and SNr
influence motor cortex
LTP/D
LTD
requires a lot of interactions
LTP
Also complex
needs NMDA
Both need DA
PFC
guiding behavior
addictive behavior
Impulsivity, reward learning, behavioral sensitization
DA
complex effect on glut
Increases LTD vs LTP at glut synapses
If applied again LTP is induced
amphetamine
withdrawal
increased response to glut and decreased to DA (inhibitory)