The Dynamic Synapse Flashcards
How can a Glutamatergic synapse be silenced or unsilenced? (What receptor is at play and what is the other one doing?)
NMDARs are always present on postsynaptic cell, and present/endocytose AMPARs depending on the signal received form the presynaptic cell
What NMDAR subunit is present in the developing synapse? What does it get swapped out for? What is a result of this?
GluN2B -> GluN2A Synapse matures (auxiliary proteins join in too, plus PSD-95)
What happens if GluN2B is understimulated? If it’s stimulated enough?
Under: Preventing addition of more AMPARs
Enough: Adds AMPARs
What is the role of SyNGAP, and what happens when it is faulty?
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
What was the final nail in the coffin to prove that there’s a difference between neonatal and adult synapses?
Neonatal and Adult synapses have different pharmacology
Ifenprodil affects neonatal synapses more, Zn affects adults more
In simple terms, what chemical reaction drives Long Term Potentiation?
AMPARs depolarize the cell, causing Mg to unblock the NMDARs, allowing Calcium to flood into the cell which drives many Calcium-dependent reactions
What enzyme is referred to as the Big Daddy of LTP?
Calmodulin Kinase 2 (CAMK2)
What is a classic sign of LTP?
More AMPAR expression
What are the two pathways of LTP seen in class?
NMDAR-dependent LTP
Presynaptic LTP
What are the 3 pathways of LTD seen in class?
NMDAR-dependent LTD
mGluR-dependent LTD
eCB-LTD
How does NMDAR-dependent LTP work?
NMDARs allow Ca in which drives CAMK to express more AMPARs
How does Presynaptic LTP work?
Increased firing rates trigger a protein cascade in the presynaptic cell that results in longer, more concentrated glutamate releases
How does NMDAR-dependent LTD work?
Ca entering the cell via NMDAR receptors bind Calcineurin and trigger the endocytosis of AMPARs
True/False? All regions of the brain have the same plasticity mechanisms
False
How can NMDARs cause both LTP and LTD?
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
How does mGluR-dependent LTD work?
Activation of mGluR1/5 triggers endocytosis of AMPARs (somehow)
How does eCB-LTD work?
endocannabinoids travel presynaptically to prevent release of NT
Define homeostatic synaptic plasticity
The way your body modulates a neurons inputs to only retain potentiated information (scales down unpotentiated neurons)
How is homeostatic scaling important for AMPAR response?
It helps regulate AMPAR response amplitude
What component of the brain is thought to have a role in synaptic scaling and how?
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
What is thought to measure Ca levels in neuron
CAMK4
Describe the example of RNA Editing seen in GluA2
The DNA codon codes for Glutamine but the codon in RNA codes for Arginine
How are KAR subunits different than AMPAR subunits in terms of modification?
KARs are “wobbly”
How does phosphorylation change the open probability of NMDARs?
50% -> 80%
