T1 L19 Synaptic plasticity in learning & memory

Question 1

What are the 2 types of memory?

Answer 1

Explicit

Implicit

Question 2

What is explicit memory?

Answer 2

Declarative memory
Facts & events
Medial temporal lobe & diencephalon

Question 3

What is implicit memory?

Answer 3

Nondeclarative memory
Procedural memory: skills & habitats
Classical conditioning - skeletal musculature & emotional responses

Question 4

What is the definition of learning?

Answer 4

Response of the brain to environmental events & involves adaptive changes in synaptic connectivity which alter behaviour

Question 5

What is Hebb’s rule?

Answer 5

Persistence or repetition of reverberatory activity tends to induce lasting cellular changes that add to its stability.
When an axon of cell A is near enough to excite a cell B & repeatedly or persistently takes part in firing it, some growth processes or metabolic changes takes place in one or both cells so A’s efficiency is increased

Question 6

Describe the process of learning behaviour

Answer 6

1) External stimulus
2) Activation of cell assembly by a stimulus
3) Reverberating activity continues after activation after stimulus is removed
4) Hebbian modification strengthens reciprocal connections between neutrons that are active at the same time
5) Strengthened connections of the cell assembly contain the engram for the stimulus
6) After learning, partial activation of the assembly leads to activation of the entire representation of the stimulus

Question 7

What are the rules of synaptic modification?

Answer 7

Cells that wire together fire together
Neurons that fire out of sync lose their link
Strengthening & weakening synaptic connections in the brain provides a means by which learning occurs & memories can be formd

Question 8

What is long term potentiation?

Answer 8

Mechanism underlying synaptic strengthening

Question 9

Where do you record high frequency electrical stimulation from?

Answer 9

The cells within the dentate gyrus

Question 10

How long is the long term potentiation produced by 1 high frequency stimulation?

Answer 10

Hours

Question 11

How long is the long term potential produced by multiple high frequency stimulations?

Answer 11

Days/months

Question 12

What is the definition of temporal in respect to LTP?

Answer 12

Summation of inputs reaches a stimulus threshold that leads to induction of LTP

Question 13

What is the definition of associative?

Answer 13

Simultaneous stimulation of a strong & weak pathway will induce LTP at both pathways (spatial summation)
Coincidence detection

Question 14

Why are long term potentiation specific?

Answer 14

LTP at 1 synapse is not propagated to adjacent synapses (input specific)

Question 15

What happens at the synapse?

Answer 15

1) Glutamate released onto inactive cell
2) AMPA receptor activated to produce EPSP
3) NMDA receptor blocked by Mg2+. Depolarisation is not sufficient to expel Mg2+

4) Glutamate released onto active cell
5) AMPA receptor activated
6) Mg2+ block on NMDA is relieved
7) Na+ moves through AMPA & NMDA channel
8) Ca2+ through NMDA channel
9) Activation of PKC & CaMKII
10) Phosphorylation of existing AMPA receptors which increases their effectiveness. Stimulates insertion of new AMPA receptors into the membrane

Question 16

Describe CaMKII molecular switch

Answer 16

Ca2+ entry through NMDA receptor leads to activation of CaMKII
CaMKII has autocatalytic activity & becomes phosphorylated
Once phosphorylated it no longer requires Ca2+
Maintains phosphorylation after depolarising stimulus has receded
Maintains increased excitability of neurons for minutes to hours

Question 17

How is nitric oxide synthase activated?

Answer 17

By Calcium diffusing through NMDA channel

Question 18

What happens once nitric oxide synthase is activated?

Answer 18

NO diffuses from site of production
Activates guanylyl cyclase in presynaptic terminal
Guanylyl cyclase produces second messenger cGMP
Signal transduction cascade leads to increased glutamate release from the synaptic buton

Question 19

What is required for long lasting LTP?

Answer 19

Protein synthesis

Question 20

What are the stages of memory formation?

Answer 20

Acquisition - training
Consolidation
Recall - testing

Question 21

What is the consequence of injecting a protein synthesis inhibitor just post-acquisition?

Answer 21

Inhibits recall which is necessary for consolidation

Question 22

What is CREB & how is it activated?

Answer 22

cAMP response element

Binding protein activated by phosphorylation by a number of kinases

Question 23

Describe early phase LTP

Answer 23

Lasts minutes to hours
Explained by Ca2+ actions through NMDA receptor & subsequent enhancement of AMPA receptor efficiency, presynaptic events etc.

Question 24

Describe late phase LTP

Answer 24

Lasts hours/days/months

Requires new protein synthesis & can involve morphological changes & establishment of new synapses

Question 25

Describe the calcium activated signal transduction cascades involved in LTP

Answer 25

Activate new protein synthesis from dendritically localised mRNAs
Filter back to cell body to stimulate new gene transcription, protein synthesis & recruitment of new proteins to the synapse

Question 26

What is long term depression?

Answer 26

Activity dependent reduction if efficacy of neuronal synapses
Opposite of long term potentiation

Question 27

What does low frequency stimulation cause?

Answer 27

Decrease in EPSP amplitude on further stimulation

Question 28

What is involved long term depression?

Answer 28

NMDA dependent process
AMPA receptors are de-phosphorylated & removed from the membrane
Prolonged low level rises in Ca2+ activate phosphases instead of kinases

Question 29

What do LTP & LTD reflect?

Answer 29

Bidirectional regulation of

1) phosphorylation
2) number of postsynaptic AMPA receptors

Question 30

What is AP5 and what does it do?

Answer 30

NMDA receptor antagonist
Blocks hippocampal LTP
Blocks learning in the Morris Water Maze

Question 31

What is the effect of alcohol on learning and memory?

Answer 31

NMDA receptor antagonist
Directly blocking normal LTP processes leads to blackouts & amnesia
Disrupts hippocampal theta rhythms & short term memory

Question 32

What are the consequences of chronic alcoholism associated with nutritional deficiency?

Answer 32

Can result in Korsakoff’s syndrome or psychosis

Loss of recent memory & tendency to fabricate accounts of recent events (confabulation)

Question 33

What is the effect of benzodiazepines on learning & memory?

Answer 33

Indirect agonist of GABA(A) receptors. Binding increases receptor affinity for GABA, increase frequency of channel opening
Anxiolytic & hypnotic drugs

Question 34

What is a side effect of benzodiazepines?

Answer 34

Anterograde amnesia

Question 35

What is the effect of cholinergic / anticholinergics on learning & memory

Answer 35

Acetylcholine projections
Basal forebrain bundle: medial septum to hippocampus. Basal nucleus to cortex
Septum to hippocampus projection regulates theta waves
Scopolamine (muscarinic receptor antagonist) suppresses theta waves & impairs spatial learning

Question 36

What can be given to treat Alzheimers?

Answer 36

Acetylcholinesterase inhibitors e.g. physostigmine

Boost cholinergic function & improve memory impairments

Question 37

Give some other learning processes which use LTP or a similar mechanism

Answer 37

Activity-dependent synaptogenesis

Motor learning e.g. riding a bike