Synaptic plasticity in learning and memory

Question 1

Learning

Answer 1

The response of the brain to environmental events and involves adaptive changes in synaptic connectivity which will in turn alter behaviour

Question 2

Rules of synaptic modification

Answer 2

Neurones that fire together wire together

Neurones that fire out of sync lose their link

Question 3

Hippocampus

Answer 3

Shape and anatomy means pathways can be easily distinguished and recorded from electrophysiologically

Question 4

Temporal

Answer 4

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

Question 5

Associative

Answer 5

Simultaneous stimulation of a strong and weak pathway will induce LTP at both pathways

Question 6

Specific

Answer 6

LTP at one synapse is not propagated to adjacent synapses

Question 7

LTP

Answer 7

Long term potential

Question 8

What happens in a synapse

Answer 8

Glutamate release on inactive cell

AMPA receptor activated to create EPSP

NMDA receptor blocked by MG2+ ion

Depolarisation from AMPA activation not sufficient to expel Mg2+

Glutamate release onto an active cell (depolarised)

AMP receptor activated

Mg2+ block on NMDA receptor relieved Na+ through AMP and NMDA channels Ca2+ through NMDA channel

Protein kinase C and CaMKII activated

Question 9

CaMKII molecular switch

Answer 9

Ca2+ entry through the NMDA receptor leads to activation of CaMKII

CaMKII has autocatalytic activity so is phosphorylated

When phosphorylated is constitutively active

Maintains phosphorylation, insertion of AMPA receptors etc after the depolarising stimulus has receded

Question 10

Presynaptic events in LTP

Answer 10

PostS neurone can feed back to PreS neurone by retrograde NT (NO)

Ca2+ through the NMDA channel activates NO synthase

NO diffuses from site of production and activates guanylyl cyclase in the PreS terminal

Guanylyl cyclase produces second messenger cGMP

Signal transduction cascade leads to increased glutamate release from the synaptic button

Question 11

Late phase LTP

Answer 11

Protein synthesis inhibitors prevent the consolidation of long term memories and LTP

Stage of memory formation (acquisition, consolidation, recall)

Protein synthesis inhibitors injected just post-acquisition inhibits recall

Question 12

Early vs late stage LTP

Answer 12

Early

• lasts a minute to an hour
• actions of Ca2+ through NMDA receptor

Late

• lasts hours, days or months
• requires new protein synthesis and can involve morphological changes

Question 13

LTD

Answer 13

Long term depression

Question 14

Long term depression

Answer 14

Low frequency stimulations cause opposite of long term potentiation

Involve

• NMDA dependent process
• AMP receptors are de-phosphorylated and removed from the membrane

Prolonged low level rises in Ca2+ activate phosphatases rather than kinases

Question 15

Alcohol

Answer 15

NMDA receptor antagonists

Blackouts and amnesia caused by drinking

Alcohol disrupts hippocampal theta rhythms and disrupts short term memory

Question 16

Korsakoff syndrom

Answer 16

Loss of recent memory and tendency to fabricate accounts of recent events

Question 17

Benzidiazepines

Answer 17

Indirect agonist of GABA(A) receptors:

• binding increases the receptor affinity for GABA
• increase frequency of channel opening
• anxiolytic and hypnotic drugs

Side effect is anterograde amnesia

Question 18

Cholinergics/ anticholingerics

Answer 18

Acetylcholine projections:

• basal forebrain bundle
• septum to hippocampus projection regulates theta waves
• scopolamine suppresses theta waves and impairs spatial learning

Question 19

Alzheimer’s disease

Answer 19

Acetylcholinesterase inhibitors

Boost cholinergic function

Improves memory impairments