Lecture 5 Synapse And Plasticity IV

Question 1

What happens when Long term depression (LTD) induction induced?

Answer 1

DECREASED Amplitude of AMPA receptor-mediated currents

Question 2

Why is long term depression needed?

Answer 2

To prevent saturation and decrease strength to maintain a dynamic range of memory

Question 3

What induces depression of a population of postsynaptic response

Answer 3

Extended periods of low frequency stimulation (LFS) (1Hz) of presynaptic axons

Question 4

LFS is not

Answer 4

Accompanied by depolarisation

Question 5

What are the properties of long term depression

Answer 5

Input specificity

Calcium influx through NMDA receptors dependency

Question 6

What can block LTD ? Give an example

What is LTP and LTD dependent on

Answer 6

NMDA receptor blockers such as APV

Level of calcium influx through NMDA receptors

Question 7

How does calcium influx into NMDA receptors trigger long term potentiation

Answer 7

High frequency stimulation or significant postsynaptic depolarisation.

Result: large calcium influx through the NMDA receptors

Question 8

How does calcium influx induce long term depression?

New question: what induces calcium influx in long term depression?

Answer 8

Low frequency stimulation which will induce a weak depolarisation which results in small calcium influx into NMDA receptors

Question 9

True/ false: AMPA receptors are activated for a longer period of time (5-15 minute) to induce the same weak depolarisation in long term depression

Answer 9

True

Question 10

Describe how calcium influx triggers long term potentiation

Answer 10

High frequency stimulation/ significant postsynaptic depolarisation -> long term potentiation -> large calcium influx through NMDA receptors

Question 11

How are protein phosphotases selectively activated?

Answer 11

Through prolonged levels of calcium influx through NMDA receptors

Question 12

Phosphotases

1. What is it?
2. What is their role in long term depression and what is the effect?

Answer 12

1. Enzymes that dephospharylate proteins
2. Dephosphorylate AMPA receptors -> remove AMPA receptors from the postsynaptic membrane (internalisation by clathrin dependent endocytosis) -> leading to less current in response to release of transmitters

Question 13

What do LTP and LTD reflect?

Explain the bi-directional and symmetrical regulation of AMPA -type glutamate receptors of Ca++ trigger in LTP and LTD

Answer 13

Bi-directional and symmetrical regulation of AMPA-type glutamate receptors

LTP : big polarisation -> increase Ca++ influx -> kinases employed

LTD: prolonged low frequency stimulation -> small amount of Ca++ -> phosphatases -> dephosphorylation

Question 14

Study of synapse plasticity (LTP/LTD) in vivo

Answer 14

• can be performed for days & months in awake, behaving animals with stable recordings
• show same characteristics in vivo as in slides
• If one side stimulated, other side acts as control (unstimulated)

Question 15

Describe the study in rats (examples of long-term memory paradigms)
Déclarative memory (humans) = spatial memory (rats)

Answer 15

Thé wildtype rats showed a decrease in time taken to get to get to platform.

Those that had their circuit disrupted or were introduced with drugs to disturb LTP & LTD did not have a significant decrease in time taken to get to the platform

Question 16

Characteristics that show that synapse plasticity (LTP/LTD) underlie memory

Answer 16

• Immense expression in all major pathways of the hippocampus
• LTP/LTD blocker agents prevent spatial learning
• genetic removal of CaMKII gene prevent LTP leading to memory deficit in rats
• shown to last for months in awake behaving animals
• Learning - movement seen of AMPARs into synapses in vivo
• Memory deficits (disease models), plasticity deficits [autism, Huntington’s disease, Down syndrome, Alzheimers]

Question 17

Why is input specificity important in synapse plasticity

Answer 17

Only the necessary synapses should be potentiated/depressed

Question 18

Memory consolidation needs some form of synapse remodelling and….

Answer 18

….synapse plasticity fits the necessary requirements to create the cellular basis of memory