Neural Mechanisms

of Learning
& Memory
Lecture 22
Neural Mechanism of Memory
 Short-term Memory

Change in neural activity

Reverberatory Circuits
 Long-Term Memory

structural change in brain

Hebb Synapse

simultaneous activity in pre- &
postsynaptic neurons ~
 Neural Plasticity
 Nervous System is malleable

learning occurs

Structural changes at synapses
 Changes in synaptic efficiency

Long-term potentiation (LTP)

Long-term depression (LTD)
 Studied in hippocampus ~
 Inducing LTP
Stimulating Record
electrode

Presynaptic Postynaptic
Neuron Neuron
Postsynaptic Potential
Single elec. stimulation
100 Hz. burst
+
Single stim.

-70mv

-
 LTP Duration
 In humans: years
 Experimentally-induced LTP

Strong, high frequency stimulation

100 Hz
 Intact animals

seconds - months
 HC slice

40 hrs ~
LTP: Molecular Mechanisms
 Presynaptic & Postsynaptic changes
 HC: Glutamate

excitatory
 2 postsynaptic receptor subtypes

AMPA-R  Na+

NMDA-R  Ca++
 Glu NT for both ~
 NMDA Receptor
 N-methyl-D-aspartate

chemically-gated

voltage-gated
 Activation requires

Membrane depolarization and

Glu bound to receptor~
 Single Action Potential
 Glu  AMPA-R

Na+ influx

depolarization
 Glu  NMDA-R

does not open

Mg++ blocks channel

no Ca++ into postsynaptic cell
 Followed by more APs ~
 Activation of NMDA-R
 Postsynaptic membrane depolarized

Mg++ dislodged

Glu binding opens channel
 Ca++ influx  post-synaptic changes

strengthens synapse ~
 Na+ Ca++

G G G
AMPA NMDA
Mg
 Na+ Ca++

G G G
AMPA NMDA
Mg
 Na+ Mg Ca++
G G
G
AMPA NMDA
 Na+ Mg Ca++

G G G
AMPA NMDA
 LTP: Postsynaptic Changes
 Receptor synthesis
 More synapses
 Shape of dendritic spines
 Nitric Oxide synthesis ~
 Before LTP

Presynaptic
Axon Terminal

Dendritic
Spine
 After LTP

Presynaptic
Axon Terminal

less Fodrin
Less resistance
Dendritic
Spine
 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 ~
NO Glu

Ca++
G G G

NO NOS Ca++
Long-term Depression: Hippocampus
 Decreased synaptic efficiency

Forgetting?
 Glutamamte-R

AMPA-R & NMDA-R
 Stimulation pattern?

1 Hz for 10-15 min

Low Ca++ influx
 Decrease # of AMPA-R

Weaker EPSPs ~
 Hippocampus: LTP vs LTD
 Same receptors

Different stimulation frequency

Different Ca++ concentrations
 LTD can reverse LTP
 LTP can reverse LTD
 Similar mechanisms in other areas

Not necessarily identical ~