Lecture 14 - Synaptic Plasticity II

Question 1

What are the two ways in which LTD can be inducted?

Answer 1

Low-Frequency Stimulation (LFS) (900 pulses at 1 Hz) or Pairing (1 Hz with mild depolarization around threshold)

Question 2

How is spike timing dependent plasticity induced?

Answer 2

Spike timing dependent plasticity coordinates presynaptic activity with postsynaptic firing.

Question 3

What happens when you continuously stimulate pre before post in spike timing dependent plasticity?

Answer 3

LTP is induced.

Question 4

What happens when you continuously stimulate post before pre in spike timing dependent plasticity?

Answer 4

LTD is induced.

Question 5

What determines the effect of STDP?

Answer 5

The relative timing of presynaptic activity (the EPSP) to the postsynaptic activity (the AP) determines the outcome.

Question 6

Between which neurons do mossy fiber synapses occur?

Answer 6

CA3 - Dentate Gyrus

Question 7

True or False?:

CA1 and CA3 LTP are NMDAR dependent.

Answer 7

False

CA1 LTP is NMDAR dependent. CA3 LTP is NMDAR independent.

Question 8

What happens if you block all glutamate receptors in mossy fiber synapses and then stimulate them with a tetanus? What does this tell you about mossy fiber LTP?

Answer 8

EPSPs will stop. As you wash out the blocker, EPSPs will return, but they will return to a level higher than that of their intial level. This indicates that mossy fiber LTP is independent of glutamate receptor activation.

Question 9

What happens if you increase the amount of calcium buffer in the CA3 cell of the mossy fiber synapse and then stimulate it with a tetanus? What does this tell you about mossy fiber LTP?

Answer 9

Nothing will happen; the tetanus will produce the same LTP. This indicates that the mossy fiber LTP is independent of post-synaptic calcium.

Question 11

What does PKA phosphorylate in mossy fiber presynaptic cells?

Answer 11

PKA phosphorylates elements of the vesicle release machinery.

Question 12

What changes intracellularly that allows for mossy fiber LTP? What does this change?

Answer 12

An increase in presynaptic Ca²⁺ increases the activity of adenylyl cyclase 1 (AC1), leading to more cAMP production, more PKA activity, and more vesicle release.

Question 13

What triggers mossy fiber LTD?

Answer 13

Glutamate triggers mGluR2 which decreases adenyly cyclase 1 (AC1) activity, leading to less cAMP, less PKA activity, and less vesicle release.

Question 14

What is the climbing fiber on a purkinke cell?

Answer 14

The climbing fire is a axon that climbs up the purkinje axon and wraps all around the purkinje dendrites.

Question 15

When are parallel fibers innervating purkinke cells plastic?

Answer 15

Parallel fibers are plastic when their activity is paired with that of the climbing fiber.

Question 16

True or False?:

Pairing cimbing fiber and parallel fiber activation leads to LTD.

Answer 16

True

Question 17

Why are climbing fibers thought to act as negative feedback?

Answer 17

While undertaking a motor learning task, if the action are not what you want, climbing fiber activity will “punish” the parallel fibers that were active when it was by depressing them. It is thought to be an error signal of sorts.

Question 18

True or False?:

Cerebellar LTD is mGluR and PKC dependent and results in the endocytosis of AMPARs.

Answer 18

True

Question 19

How does climbing fiber depolarization lead to LTD?

Answer 19

Climbing fiber depolarization results in an influx of calcium to the dendritic spine. The calcium (combined with calcium released from the ER through G_q signaling) and diacylglycerol (DAG) (also from G_q signaling) activate phosphokinase C (PKC), which phosphorylates substrate proteins that internalize AMPA receptors.

Question 20

Which pathway is triggered by mGluR that leads to LTD in cerebellar LTD?

Answer 20

G_q Pathway

Question 21

Which types of depression can endocannabinoids cause?

Answer 21

DSI (depolarization-dependent suppression of inhibition), DSE (depolarization-dependent suppression of excitation), and LTD (long-term depression)

Question 22

What are endocannabinoid-mediated DSI and DSE and how does they occur?

Answer 22

Depolarization-dependent suppression of inhibition (DSI) and depolarization-dependent suppression of excitation (DSE) are two forms of synaptic plasticity of GABAergic and glutamatergic synapses, respectively. They are caused by calcium contreation increases in the postsynaptic cells and are mediated by the release of a retrograde endocannabinoid messenger which inhibits synapses via presynaptic mechanisms that inhibit neurotransmitter release.

Question 23

True or False?:

CB1 dependent LTD is the result of postsynaptic AMPAR endocytosis.

Answer 23

False

CB1 dependent LTD is the result of a decrease in release probability.

Question 24

True or False?:

Learning in general is thought to occur by GABAergic synapses.

Answer 24

False

Learning in general is thought to occur by glutamatergic synapses.

Question 25

True or False?:

Substances that trigger more dopamine response out of the VTA into the NAc are the key trigger for the development of addictions.

Answer 25

True

Question 26

What plasticular effect does cocaine exposure have in the VTA? How long does this last?

Answer 26

LTP; a few days

Question 27

What effect does chronic cocaine exosure have in the NAc? How long will this last?

Answer 27

Chronic cocaine exposure results in strenghtening of glutamatergic synapses in the NAc. This will last for months (or longer).

Question 28

True or False?:

Weakening of glutamatergic synapses in the NAc suppresses cocaine-induced behaviour.

Answer 28

True

Question 29

True or False?:

LTP and LTD are Hebbian forms of synaptic plasticity.

Answer 29

True

Question 30

What is the result of homeostatic synaptic plasticity for excitatory and inhibitory synapses?

Answer 30

When an excitatory cell has low activity, more glutamate receptors will go to the synapse to increase the cell’s ability to detect glutamate and receive EPSPs. When an inhibitory cell has low activity, less GABA receptors will go to the synapse to decrease the cell’s ability to detect GABA and receive IPSPs. When an excitatory cell has high activity, less glutamate receptors will go to the synapse to decrease the cell’s ability to detect glutamate and receive EPSPs. When an inhibitory cell has high activity, more GABA receptors will go to the synapse to increase the cell’s ability to detect GABA and receive IPSPs.