The Dynamic Synapse

Question 1

How can a Glutamatergic synapse be silenced or unsilenced? (What receptor is at play and what is the other one doing?)

Answer 1

NMDARs are always present on postsynaptic cell, and present/endocytose AMPARs depending on the signal received form the presynaptic cell

Question 2

What NMDAR subunit is present in the developing synapse? What does it get swapped out for? What is a result of this?

Answer 2

GluN2B -> GluN2A
Synapse matures (auxiliary proteins join in too, plus PSD-95)

Question 3

What happens if GluN2B is understimulated? If it’s stimulated enough?

Answer 3

Under: Preventing addition of more AMPARs
Enough: Adds AMPARs

Question 4

What is the role of SyNGAP, and what happens when it is faulty?

Answer 4

Protein that gets activated/inactivated by Ras, activation leads to increase in ERK1/2 which in turn increases number of Synaptic GluRs

Faulty SynGAP is seen in autism

Question 5

What was the final nail in the coffin to prove that there’s a difference between neonatal and adult synapses?

Answer 5

Neonatal and Adult synapses have different pharmacology

Ifenprodil affects neonatal synapses more, Zn affects adults more

Question 6

In simple terms, what chemical reaction drives Long Term Potentiation?

Answer 6

AMPARs depolarize the cell, causing Mg to unblock the NMDARs, allowing Calcium to flood into the cell which drives many Calcium-dependent reactions

Question 7

What enzyme is referred to as the Big Daddy of LTP?

Answer 7

Calmodulin Kinase 2 (CAMK2)

Question 8

What is a classic sign of LTP?

Answer 8

More AMPAR expression

Question 9

What are the two pathways of LTP seen in class?

Answer 9

NMDAR-dependent LTP

Presynaptic LTP

Question 10

What are the 3 pathways of LTD seen in class?

Answer 10

NMDAR-dependent LTD
mGluR-dependent LTD
eCB-LTD

Question 11

How does NMDAR-dependent LTP work?

Answer 11

NMDARs allow Ca in which drives CAMK to express more AMPARs

Question 12

How does Presynaptic LTP work?

Answer 12

Increased firing rates trigger a protein cascade in the presynaptic cell that results in longer, more concentrated glutamate releases

Question 13

How does NMDAR-dependent LTD work?

Answer 13

Ca entering the cell via NMDAR receptors bind Calcineurin and trigger the endocytosis of AMPARs

Question 14

True/False? All regions of the brain have the same plasticity mechanisms

Answer 14

False

Question 15

How can NMDARs cause both LTP and LTD?

Answer 15

By activating different proteins (CAMK2 and Calcineurin respectively)
The two proteins require different levels of calcium in the cell, which depends on cell firing
Therefore, depending on the amount of cell firing, NMDARs drive either LTP or LTD

Question 16

How does mGluR-dependent LTD work?

Answer 16

Activation of mGluR1/5 triggers endocytosis of AMPARs (somehow)

Question 17

How does eCB-LTD work?

Answer 17

endocannabinoids travel presynaptically to prevent release of NT

Question 18

Define homeostatic synaptic plasticity

Answer 18

The way your body modulates a neurons inputs to only retain potentiated information (scales down unpotentiated neurons)

Question 19

How is homeostatic scaling important for AMPAR response?

Answer 19

It helps regulate AMPAR response amplitude

Question 20

What component of the brain is thought to have a role in synaptic scaling and how?

Answer 20

Glia
Act as an early warning system, detect when there’s not a lot of glutamate going around and release TNFalpha to scale up excitatory synapses

Question 21

What is thought to measure Ca levels in neuron

Answer 21

CAMK4

Question 22

Describe the example of RNA Editing seen in GluA2

Answer 22

The DNA codon codes for Glutamine but the codon in RNA codes for Arginine

Question 23

How are KAR subunits different than AMPAR subunits in terms of modification?

Answer 23

KARs are “wobbly”

Question 24

How does phosphorylation change the open probability of NMDARs?

Answer 24

50% -> 80%