Module 10 - Lecture 7 - Plasticity

Question 1

What is the “big picture” of what changes with neural plasticity?

Answer 1

Definition of plasticity for our purposes:

How can we modify the neural pathways, the synaptic connections between neurons? Plasticity is how we can change the strength of the connections/change the way that pathways are fundamentally interacting with one and another to convey information in response to experience or injury.

The big picture of synaptic plasticity is that the connections between neurons are dynamic and modifications happen in order to strengthen or weaken a synaptic connection. The effect could be short-term (msec) to long term (years)

Question 2

What changes for “short-term plasticity”? (Pre or postsynaptic?)?

Answer 2

Short-term plasticity are changes in synaptic strength on the PRE-synaptic side. It is increasing the neurotransmitter release!!!

Question 3

Name the 4 forms of “short term plasticity”.

Which ones strengthens the connection?

Which ones weaken the connection?

Answer 3

1. Facilitation –> strengthen
2. Depression –> weaken
3. Augmentation –> strengthen
4. Potentiation –> strengthen

Question 4

What is the mechanism that explains facilitation = short term plasticity?

What is the duration of the effect?

Answer 4

Facilitation = Synaptic facilitation is a rapid increase in synaptic strength that occurs when two or more action potentials invade the presynaptic terminal within a few milliseconds of each other.

Mechanism = the general idea is to release more neurotransmitters when there is a build-up of calcium !!!!
When you have 2 AP arrive very close to one another (10-20 msecs), the calcium which would have to be actively pumped out it may still not have been fully removed from the presynaptic terminal.
When a second AP arrives there is still some residual calcium left… and that additional calcium is added to the calcium that is also released because of this second AP.
More calcium = more vesicle binding which results in a higher number of quanta released and that is an increase in neurotransmitters released.
BUT after a brief period of time = that extra calcium would be actively pumped out = this is the reason why facilitation only works over a short period of time.

Duration = can last tens of msecs.

Question 5

What is the mechanism that explains depression = short term plasticity?
What is the duration of the effect?

Answer 5

Depression = Opposing facilitation is synaptic depression, which causes neurotransmitter release to decline during sustained synaptic activity.

Mechanism = With chronic/prolonged stimulation the post-synaptic change in the receptor potential would in fact start to decrease which is MORE DEPRESSION and less of a change in the receptor potential which is a decrease in synaptic strength. With this progressive activation, you run out of vesicles to release because there is a progressive decrease in the pool of synaptic vesicles available. Therefore, there is a time period of waiting for the biochemical processes to form more vesicles, you run out of transmitters for a few seconds until the neurotransmitter is resynthesized.

Duration = a few seconds

Question 6

What is the mechanism that explains augmentation = short term plasticity?
What is the duration of the effect?

Answer 6

Augmentation = A form of synaptic plasticity that is elicited by repeated synaptic activity and serves to increase the amount of neurotransmitter released from presynaptic terminals.

Mechanism = Due to prolonged elevations of calcium in the presynaptic terminal, it improves the ability of the synaptic vesicles to fuse with the pre-synaptic membrane and increase the amount of transmitter released.

Duration = seconds

Question 7

What is the mechanism that explains potentiation = short term plasticity?
What is the duration of the effect?

Answer 7

Potentiation = A form of synaptic plasticity that is elicited by repeated synaptic activity and serves to increase the amount of neurotransmitter released from presynaptic terminals.

Mechanism = Due to prolonged elevations of calcium in the presynaptic terminal, it improves the ability of the synaptic vesicles to fuse with the pre-synaptic membrane and increase the amount of transmitter released.

Duration = Tens of seconds to minutes

Question 8

What is the idea of “biological importance”?

Answer 8

Biological importance = Presynaptic and postsynaptic cells can dynamically change their signaling behavior based on their internal state or the cues they receive from other cells. This type of plasticity, or capacity for change, makes the synapse a key site for altering neural circuit strength and plays a role in learning and memory.

Question 9

What is the idea of “habituation” and what does it represent?

Answer 9

Habituation = A decrease in response to a stimulus that is repeated/of on interest (clothing example). It results from a decrease in presynaptic transmitter release.
Habituation there is some behavioral change because you have learned that there is less biological importance to the stimuli.

Question 10

What is the idea of “Sensitization” and what does it represent?

Answer 10

Sensitization = The return of the response due to a new stimulus (a painful shock). It results from the recruitment of additional circuits. In fact, in sensitization, a change at one synapse results in a change at a different synapse which is called heterosynaptic plasticity.

Question 11

What is the essential processes necessary for long-term plasticity. In general what happens?

Answer 11

Long term plasticity is systematically being able to strengthen a synaptic connection
To change synaptic plasticity on a time-scale larger than a few hours, maybe years - permanent, it requires :
- Gene transcription
- Protein synthesis
- Synaptic growth

Question 12

What are the 3 properties of long-term potentiation (LTP)?

Answer 12

1. Specificity
2. Associativity
3. State-dependent

Question 13

What is specificity = LTP?

Answer 13

Specificity = LTP in one synapse does not occur in other, inactive synapses that contact the same postsynaptic neuron

The idea that if you had a strong synapse, which is able to induce the post-synaptic neuron to have a large change in its receptor potential, that pathway alone would get stronger. However, an inactive pathway, pathway 2 in the example, is not getting stronger.

Question 14

What is associativity = LTP?

Answer 14

Associativity = If a weak stimulation of a neural pathway is accompanied by strong stimulation in a pathway that is close, both synapses will have LTP.
Pathway 1 is still strong and stimulation very often and pathway 2 is stimulated in a periodic manner here and there. Pathway 2 is associated with pathway 1 and benefits from their association to get stronger.

In fact, the majority of our learning is done by developing these associations !!!
***NOTICE the difference in 1 and 2 is inactive pathway 2 and weak stimulation pathway 2

Question 15

What is state-dependent = LTP?

Answer 15

State-dependent = Single stimulus would not normally result in LTP. If a single stimulus paired with strong depolarization of the postsynaptic neuron, LTP will occur.
A hybrid between specificity and associativity = the strengthening of these specific synapses will only occur if the single stimulus is able to depolarize the postsynaptic neuron about a 100 milliseconds following when the neurotransmitter was released from the pre-synaptic side to cause that change in the receptor potential.
We only strengthen pathways that have that meaningful effect to give that biological importance.

Question 16

What is the mechanism by which long-term potentiation occurs at a specific post-synaptic connection (the neurotransmitter used, the receptor that drives the process, the ion necessary, and what receptor changes)?

Answer 16

Mechanism = High-frequency stimulation → AMPA receptors open Na+ flows → NMDA receptors open and Na+ and Ca2+ flow → presence of intracellular Ca+ produces LTP → the Ca2+ acts as a secondary messenger → an increase in intracellular calcium results in more AMPA receptors to be added to the postsynaptic membrane = This results in an increase to the response of the postsynaptic neuron to glutamate release and in the strengthening of synaptic transmission which is the maintenance of LTP.

***The AMPA receptors need to be there to allow for the calcium to enter the membrane, but it is these added AMPA receptors that will allow for more regional depolarization that can strengthen the synapse and increase the likelihood to reach the threshold and induce an AP.

The neurotransmitter used = NMDA receptors need both glutamate and membrane depolarization (because of Mg2+ that blocks the channel)
The receptor that drives the process = LTP depends on NMDA glutamate receptors
The ion necessary = Sodium and calcium
What receptor changes = AMPA receptors are added to the postsynaptic membrane

Question 17

What is a secondary change that occurs with LTP (tip the cytoskeleton or buds)?

Answer 17

The secondary change that occurs with LTP = Areas with a lot of calcium will remodel the cytoskeleton and overtime if the synapse is strong, what starts to happen is you will start to experience more “buding” = more pronounced surface area and more pronounced connection of the post-synaptic side to where it will receive neurotransmitters from the pre-synaptic terminal = more binding sites and this physical change in the dendrites.

Question 18

Understand or logically guess what consequence of LTP is on the size of a post-synaptic potential…?

Answer 18

With an increase in intracellular calcium this results in several biochemical events = consequence is LTP = Increase in the number, size and length of dendrites spines (glutamatergic) + increase in the number of binding sites for glutamate.

Question 19

What is the mechanism behind Long-term-depression (LTD)?

Answer 19

If a synapse has no longer a form of biological importance → we can make it so that the change in the receptor potential is not as profound as it used to be = selectively weaken synapses = Long term depression

Mechanism = image

Question 20

What is the direction of “spike timing dependence”? How is the timing between the generation of a receptor potential and an action potential are involved for LTP or LTD?

Answer 20

“Cells that fire together, wire together”
Synapses that successfully activate the postsynaptic neuron should be strengthened
Synapses that are not successful in activating the postsynaptic neuron should be weakened.

Long term potentiation = If the presynaptic activity occurs BEFORE the postsynaptic activity = this synapse is strengthened
If the receptor potential causes action potential, passive flow of action potential can further depolarize specific (with glutamate) ligand gated NMDA receptors (passive back flow) which is a cause and effect relationship.

Long term depression = If the presynaptic activity occurs AFTER the postsynaptic activity = this synapse is weakened

Question 21

What is the general difference between homosynaptic and heterosynaptic plasticity (receptors used and specificity)?

Answer 21

Homosynaptic plasticity = Changes in synaptic strength localized to post-synaptic target neurons stimulated by the pre-synaptic neuron. (ligand-gated receptors)

Heterosynaptic plasticity = The activity of a neuron leads to unspecific changes in the strength of synaptic connections from other neurons. Interneurons release other neurotransmitters (serotonin/dopamine/ACh) that act on the synapse via G-protein coupled receptors

Question 22

Appreciate and understand the big picture of plasticity, how it is involved in repair (what does it look for?), how can the micro mechanism you learned leads to macro changes?

Answer 22

Gross remodeling = is the fact that we can change our connectivity
In our primary sensory cortex –> there is somatotropic representation = some regions of our sensory cortex correspond to specific body parts.
What can happen is because we can change the conductivity of neurons and what they are able to excite, you can change the functional relevance of a neuron through experience

For example:
Just looking at the way the MRI activity of the brain…NOTICE
BEFORE = when the individual started learning the task = making more errors = there was more cortical activity
AFTER = when the individual engaged with the task = making fewer errors = the amount of cortical activity started to decrease.
This corresponds to the neurons of the area requiring less oxygen, in order for them to be excited.
What could explain that? Long term potentiation means that we have a stronger synapse with time I am more efficient, need less energy because having one AP is enough to elicit excitation of maybe other parts of my brain to execute the motor task.
More metabolically efficient in the brain.