Post on 31-Dec-2015
transcript
Neural Plasticity:Long-term
PotentiationLesson 15
Neural Plasticity Nervous System is malleable
learning occurs Structural changes at synapses
Changes in synaptic efficiency Long-term potentiation Long-term depression
LTP & LTD throughout brain Many different mechanisms ~
Neural Mechanism of Memory
Donald Hebb Short-term Memory
Change in neural activity not structural temporary
Reverberatory Circuits - cortical loops of activity ~
Reverberating Loops
Maintains neural activity for a period Activity decays ~
Hebb’s Postulate
Long-Term Memory required structural change in brain relatively permanent
Hebb Synapse use strengthens synaptic efficiency concurrent activity required
• pre- & postsynaptic neurons ~
Long-term Potentiation
According to Hebb rule use strengthens synaptic connection
Synaptic facilitation Structural changes Simultaneous activity
Experimentally produced hippocampal slices associative learning also ~
Inducing LTP
Stimulating electrode
Record
Presynapticneuron
Postsynapticneuron
-70mv
-
+
Postsynaptic Potential
1. Single Stimulation (AP)
2. High frequency stimulation
3. Single stimulation
Pattern Of Stimulation Brief, high frequency stimulation > 10 Hz (10 AP/sec)
LTP Duration Hippocampal slices: 40 hours Intact animals: Up to a year ~
Experimentally-induced LTP
Associative learning Respondent & Operant learning
Strengthening of association Strong link: US Response (UR) Weak link: CS Response (CR)
Concurrent activity CS, US Response LTP in CS (strengthened)~
LTP & Associative Learning
W1
W2
S R
W1
W2
SUS
LTP: Associative Before Learning
Stim S AP in R W1 or W2 no AP in R
W1
W2
S R
W1
W2
SUS
LTP: Associative Induction
Paired: S + W1 AP
• LTP in W1
Unpaired: W2 no AP
W1
W2
S R
W1
W2
SUS
LTP: Associative After LTP
W1 alone AP in R
W2 alone no AP in R
LTP: Molecular Mechanisms
Presynaptic & Postsynaptic changes HC Glutamate
excitatory 2 postsynaptic receptor subtypes
AMPA Na+ NMDA Ca++
Glu ligand for both ~
NMDA Receptor
N-methyl-D-aspartate Glu binding opens channel?
required, but not sufficient Membrane must be depolarized
before Glu binds ~
Single Action Potential
Glu AMPA-amino-3-hydroxyl-5-methyl-4-
isoxazole-propionate depolarization
Glu NMDA does not open Mg++ blocks channel Little Ca++ into postsynaptic cell
Followed by more APs ~
AMPA NMDAMg
G
Ca++Na+
G GG
NMDAMg
G
Ca++
GAMPA
Na+
GG
NMDA
MgG G
Ca++
AMPA
Na+GG
NMDAG
Ca++
G
Mg
AMPA
Na+
GG
Activation of NMDA-R
Ca++ channel chemically-gated voltage-gated
Mg++ blocks channel Ca++ influx post-synaptic changes
strengthens synapse ~
Ca2+-mediated Effects
Activation of protein kinases Protein Kinase C (PKC) Ca2+/calmodulin-dependent protein
kinase (CaMKII) Targets: AMPA-R & other signaling
proteins CaMKII important role
Block CaMKII No LTP Self-phosphorylation LTP duration ~
LTP: Postsynaptic Changes
Receptor synthesis More synapses Shape of dendritic spines Nitric Oxide synthesis ~
PresynapticAxon Terminal
Dendritic Spine
Before LTP
PresynapticAxon Terminal
Dendritic Spine
After LTP
less Fodrin
Less resistance
Nitric Oxide - NO
Retrograde messenger Hi conc. poisonous gas
Hi lipid solubility storage?
Synthesis on demand Ca++ NO synthase NO
Increases NT synthesis in presynaptic neuron more released during AP ~
G Ca++
G
Ca++NOSNO
NO cGMP Glu
GG