Long Term Potentiation

Question 1

What is retrograde signalling?

Answer 1

neurotransmitters that signal the pre-synaptic neuron based on post-synaptic response

Question 2

Does glutamate open NDMA channels?

Answer 2

Yes, but ions are not able to flow through because of the magnesium channel blocker

Question 3

During the process of long term potentiation, what is Pavlov’s dog learning about the association with food and the other stimuli around it?

Answer 3

1. that the tone reliably predicts food

2. that no other stimuli reliably predicts food

Question 4

Why does food create a stronger excitatory response?

Answer 4

Because it is unconditioned, and the response is present before learning occurs

Question 5

What is the first step in the LTP process, using Pavlov’s dog as an example?

Answer 5

1. Ringing the bell causes glutamate to be released on to post-synaptic neurons (binding to both AMPA and NMDA, opening both AMPA and NMDA channels, but ion flow only happens at AMPA receptor site)
   - some depolarization occurs at post-synaptic site of AMPA receptor, but signal is not strong enough for excitation to propagate to axon hillock

Question 6

What is the second step in the LTP process?

Answer 6

2. Presentation of food causes Na+ propagation all the way to the axon hillock and causes an action potential to fire

Question 7

What is the third step in the LTP process?

Answer 7

3. If tone neuron is fired at the same time as the food neuron, or immediately before, the combined excitatory effect of both stimuli has an even greater depolarizing effect than either one of them on their own (because glutamate is released on to a synapse that is already slightly depolarized by the tone)

Question 8

What is the fourth step in the LTP process?

Answer 8

4. Magnesium pops out of the NMDA receptor because now the net charge of the inner membrane is positive (due to stronger depolarization)
   * in order for magnesium to be displaced, unblocking the channel, the NMDA receptor has to be open (which means that glutamate has to be bound to it) and the membrane has to be depolarized slightly when glutamate does bind

Question 9

What key ion flows through NMDA receptors after it is unblocked?

Answer 9

Ca2+

Question 10

What is the cascade of events that occurs after the NMDA channel has been unblocked?

Answer 10

1. NMDA channel becomes unblocked
2. Calcium flows into the post-synaptic membrane
3. Ca2+ causes a second messenger cascade that changes transcription

Question 11

What two transcription changes does Ca2+ cause when it flows through NMDA receptors?

Answer 11

1. it produces more AMPA receptors on the post-synaptic membrane (on the tone neuron) to increase flow of Na+, thus increasing excitability
2. it increases the post-synaptic area of the tone neuron, to give more room for new AMPA receptors such that now the AMPA receptor is excitable to cause an action potential on its own

Question 12

What is the final step of long term potentiation?

Answer 12

Pre-synaptic AMPA receptor releases more glutamate due to the retrograde signalling mechanism of nitric oxide

Question 13

Where is the mechanism of LTP concentrated?

Answer 13

In the hippocampus

Question 14

What is nitric oxide?

Answer 14

A retrograde signalling compound that causes pre-synaptic neuron to increase the release of glutamate

Question 15

What lifestyle habit can we adopt to strengthen the LTP process?

Answer 15

Getting a good night of sleep

Question 16

Why aren’t there a lot of drugs that target NMDA receptors?

Answer 16

Because these drugs would cause too much glutamate to be released, and the cells would experience excitotoxicity

Question 17

Although most drugs do not target the NMDA receptors, what is one example of a drug that inhibits aspects of the NMDA receptor?

Answer 17

PCP

Question 18

What is ketamine?

Answer 18

A substance traditionally used as an anesthetic, but also used as a club drug (called “Special K”)
- ketamine binds to the PCP binding site on the NMDA receptors

Question 19

What is exciting research into ketamine suggesting?

Answer 19

That it can significantly improve treatment-resistant depression (can take effect in as short of a time as one dose)

Question 20

Why isn’t more research into ketamine being done to help relieve depression?

Answer 20

because ketamine isn’t patented, and so pharmaceutical companies don’t want to spend money researching something they can’t make a profit off of

Question 21

What is long term depression (LTD)?

Answer 21

When the pre-synaptic neuron fires but there is no post-synaptic response (example: if the room neuron fired every time the salivation neuron did not fire, the connection would be completely lost)

Question 22

What is PCP?

Answer 22

A psychedelic drug similar to acid