Learning and memory in mammals 2

Question 1

Persistent neural activity

Answer 1

Working memory in prefrontal cortex (PFC)
Changes in PFC neuronal membrane properties (Ca2+ activated non-selective cation channels insert into membrane)
Alterations in communication between local neurons to promote recurrent firing

Question 2

LTM formation

Answer 2

Does not depend on persistent neuronal firing

Changes in strength of synaptic connections (synaptic plasticity)

Question 3

Long term potentiation

Answer 3

Long lasting activity-dependent changes in synaptic strength generated by high frequency stimulation (HFS) of presynaptic neuron
Well characterised in hippocampus

Question 4

Hippocampal electrophysiology

Answer 4

Schaffer collateral neurons stimulated with HFS
Response recorded in CA1 hippocampal subfield
Response measured as field potential (depolarisations) or action potentials (neuronal firing)

Question 5

Excitatory synapses

Answer 5

LTP at glutamatergic synapses is dependent on NMDA and AMPA receptors
NMDA blocked by Mg2+ in basal conditions, preventing cation influx
Glutamate acts on AMPA receptors to depolarise post-synaptic cell, allowing Na+/K+ influx

Question 6

NMDA-R dependent LTP

Answer 6

High presynaptic activity (HFS) causes strong depolarisation in post-synaptic dendrite
Releases Mg2+ block on NMDA-R, allowing large Ca2+ influx
NMDA-R must have glutamate bound and post-synaptic depolarisation (coincidence detectors)

Question 7

Intracellular Ca2+ in LTP

Answer 7

Stimulates intracellular signalling cascades (protein kinases and CREB)
CREB signalling promotes generation of retrograde signalling molecules (enhance neurotransmitter release)
CAMKII promotes integration of additional AMPA receptors into dendritic membrane
Synapse is strengthened as more presynaptic neurotransmitter and more AMPA receptors on post-synapse

Question 8

NMDA-R antagonist

Answer 8

DL-AP5 blocks LTP in hippocampus
Slows acquisition phase in water maze
Animals still able to learn task

Question 9

Early/late phase LTP

Answer 9

Induction (HFS)
Early LTP (1-3 hours). No protein synthesis, cAMP or PKA activation
Late LTP (2-24 hours). Requires cAMP and PKA activation
Changes in gene transcription (PKA pathway)
Protein synthesis
Growth of new synaptic connections between neurons

Question 10

Associative LTP

Answer 10

Neuron has specific threshold for LTP induction
One input stimulation may not induce LTP
Stimulating two independent projections to a neuron at lower frequencies induces LTP
May explain conditioning

Question 11

LTD

Answer 11

Long, low frequency stimulation of Schaffer collaterals decreases size of response in CA1
Modest post-synaptic depolarisation
NMDA-R Mg2+ block release is less effective
Lower Ca2+ influx into post-synaptic membrane
CAMKII not activated
AMPA removed from membrane

Question 12

Dissociative LTD

Answer 12

Asynchronous inputs onto a neuron

May keep neural networks not processing associated information separate

Question 13

Newly born neurons

Answer 13

Born in dentate gyrus (DG) of hippocampus (neurogenesis)
Higher sensitivity to LTP
Genetic ablation of neurogenesis impairs performance in Morris water maze

Question 14

Memory consolidation

Answer 14

Temporary, labile memory transformed to stable long-lasting memory
Hippocampus guides reorganisation of information in neocortex (permanently stored)

Question 15

Cav1.2 hypofunction

Answer 15

Induces deficit in memory consolidation
Mutations in Cav1.2 gene Cacna1c increase risk of schizophrenia and bipolar disorder
Mutated mice show reduced activity in hippocampus