Synaptic plasticity in learning and memory

Question 1

What is the explicit memory?

Answer 1

Facts

Events

Question 2

What is the implicit memory?

Answer 2

Procedural memory of skills and habits

Classical conditioning - Skeletal musculature and Emotional response

Question 3

Define learning

Answer 3

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

Question 4

What is meant by wiring?

Answer 4

The way in which our neurons are connected by snaptic connections
These are plastic and malleable so can be changed

Question 5

What did hebb say about learning and memory?

Answer 5

Cell assembly - neurons connected by reciprocal connections between neurons
External stimulus causes activation of the cell assembly
If activation of the cell assembly occurs for long enough consolidation occurs by a growth process and the reciprocal connections are made more effective. The neurons become wired together - permanent modification of the cell assembly.
If only part of the cell assembly is activated later, the strengthened connections could cause the whole assembly to become activated. The entire stimulus may be recognized from just part of it

Question 6

What rules of synaptic modification exist?

Answer 6

Neurons that fire together wire together

Neurons that fire out of sync lose their link

Question 7

How are learning and memories formed?

Answer 7

Strengthening and weakening of synaptic connections

Question 8

Give the effect of stimulation of an individual hippocampal neuron before and after learning

Answer 8

May not be enough to crease an EPSP great enough to fire an action potential before learning but after repetition it will elicit an action potential

Question 9

What is long term potentiation (LP)?

Answer 9

Mechanism underlying synaptic strengthening
Hippocampus
Also studied in other brain areas

Question 10

What does one high frequency electrical stimulation lead to?

Answer 10

LTP lasting hours

Question 11

What do multiple high frequency electrical stimulation lead to?

Answer 11

Lasts days and months

Question 12

Why is long term potentiation temporal?

Answer 12

Summation of inputs reaches a stimulus threshold that leads to the induction of LTP. e.g. Repetitive stimulation (HFS)

Question 13

Why is long term potentiation associative?

Answer 13

simultaneous stimulation of a strong and weak pathway will induce LTP at both pathways. (Spatial summation)
Coincidence detection
“Cells that fire together wire together”

Question 14

Why is long term potentiation specific?

Answer 14

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

Question 15

What happens at the synapse?

Answer 15

Glutamate released onto inactive cell
AMPA receptor activated to cause early phase EPSP
NMDA receptor blocked by Mg2+ and depolarization from AMPA activation is not sufficient to expel Mg2+

High frequency stimulation leads to high amounts of glutamate released onto active cell (membrane depolarized). AMPA receptor activated and Mg2+ block on receptor relieved. Na+ through AMPA and NMDA channels. Ca2+ through NMDA receptor,
Ca2+ entry through NMDA receptor activate PKC and CaMkII

Question 16

What do PKC and CaMKII do?

Answer 16

Phosphorylate existing AMPA receptors, increasing their effectiveness
Stimulate the insertion of new AMPA receptors in the membrane. LTP

Question 17

What does CaMKII do?

Answer 17

Sustained activity after repolarization
Autocatalytic activity - becomes phosphorylated
Constantly active - no longer requires Ca2+
Maintains phosphorylation, insertion of AMPA receptors after depolarisation has receded
Molecular switch which maintains increased excitability of neuron for minutes to hours

Question 18

How is Nitric oxide used in long term potentiation?

Answer 18

Postsynaptic neuron feeds back to presynaptic neuron by retrograde neurotransmitter NO

Ca2+ through NMDA channel activates Nitric oxide synthase

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

Guanylyl cyclase produces cGMP

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

Question 19

List the stages of memory formation

Answer 19

Acquisition (training)
Consolidation
Recall (testing)

Question 20

What is protein synthesis required for?

Answer 20

Long lasting LTP

Consolidation of long term memories

Question 21

What is CREB?

Answer 21

cAMP Response Element Binding protein activated by phosphorylation by a number of kinases (PKA, CaMKII etc)

Question 22

What is early phase LTP?

Answer 22

lasts a minute to an hour and can be explained by the actions of Ca2+ through the NMDA receptor and subsequent enhancement of AMPA receptor efficiency, presynaptic events etc.

Question 23

What is late phase LTP?

Answer 23

lasts hours, days or months
-requires new protein synthesis
 and can involve morphological
 changes and the establishment
 of new synapses

Question 24

What do Ca2+ activated signal transduction cascades do?

Answer 24

activate new protein synthesis from
dendritically localized mRNAs

filter back to the cell body to
stimulate new gene transcription (CREB -mediated), protein synthesis
and recruitment of new proteins to the synapse

Question 25

What is long term depression?

Answer 25

Process of forgetting
Low frequency stimulation causes a decrease in EPSP amplitude
NMDA dependant process
AMPA receptors are dephosphorylated and removed from the membrane
Prolonged low level rises in Ca 2+ activates phosphatases rather than kinases

Question 26

LTP and LTD reflect bidirectional regulation of …

Answer 26

1. phosphorylation

2. number of postsynaptic AMPA receptors

Question 27

How is the LTP and LTD hypothesis proved?

Answer 27

AP5 infused into hippocampus of rats shows no memory of morris water maze

Question 28

Describe the effect of alcohol on learning and memory

Answer 28

NMDA receptor antagonist (as well as other sites)

Blackouts and amnesia caused by drinking - directly blocking normal LTP processes?

Alcohol disrupts hippocampal theta rhythms and disrupts short term memory.

Chronic alcoholism and associated nutritional deficiency can result to Korsakoff syndrome or psychosis: loss of recent memory, and tendency to fabricate accounts of recent events (confabulation).

Question 29

Describe the effect of barbiturates on learning and memory

Answer 29

Indirect agonist of GABAA receptors:

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

Side effect to anxiolytic and sedative properties:
- anterograde amnesia

Question 30

Describe the effect of cholinergics and anticholinergics on learning and memory

Answer 30

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 and impairs spatial learning

Question 31

What drug is used in alzheimer’s?

Answer 31

Acetylcholinesterase inhibitors
(e.g. physostigmine)
Boost cholinergic function
Improves memory impairments

Question 32

What is the effect of acetylcholinesterase inhibitors in a healthy brain?

Answer 32

Controversial as to whether they improve memory
May increase attention

Most cognitive enhancing effects of both acetylcholinesterases and other cholinergic drugs, e.g. nicotine, seen in impaired subjects, i.e. Alzheimer’s patients, or in restoring performance of animals with lesions.

Question 33

What other learning processes use LTP?

Answer 33

Activity dependent synaptogenesis (development)

Motor learning - e.g. riding a bike - cerebellar