Chapter 8 - Synaptic Plasticity

Question 1

Which different types of short-term synaptic plasticity do we know of?

Answer 1

1. Facilitation
2. Augmentation
3. Potentiation
4. Depression.

Question 2

Which different types of long-term synaptic plasticity do we know of?

Answer 2

1. Long-term potentiation (LTP)

2. Long-term depression

Question 3

What is synaptic facilitation?

Answer 3

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.

Question 4

What is the mechanism behind synaptic facilitation?

Answer 4

The mechanisms that return Ca2+ to resting levels are much slower than those that cause Ca2+ to enter the synaptic terminal. Two rapidly succeeding action potentials enables a build-up of Ca2+, and thus even more neurotransmitter release.

Question 5

What is synaptic depression?

Answer 5

Synaptic depression is a decrease in synaptic strength that occurs during sustained synaptic activity.

Question 6

What is the mechanism behind synaptic depression?

Answer 6

Synaptic depression is caused by progressive depletion of a pool of synaptic vesicles that are available for release: when rates of release are high, these vesicles deplete rapidly and cause a lot of depression; depletion slows as the rate of release is reduced, yielding less depression.

Question 7

What do we know about potentiation and augmentation?

Answer 7

They both enhance the ability of incoming calcium ions to trigger fusion of synaptic vesicles with the plasma membrane, but they work over different time scales.

Question 8

What justifies a generalization of plasticity in simple nervous systems to plasticity in humans?

Answer 8

The assumption is that plasticity is so fundamental that its essential cellular and molecular underpinnings are likely to be conserved in the nervous system of very different organisms.

Question 9

What is the Aplysia californica?

Answer 9

The Aplysia californica is a sea slug that is found on the pacific coast of California and northwestern Mexico. When it is considerably disturbed, the slug is capable of releasing two different kinds of ink from different locations within its mantle cavity.

Question 10

Who is Eric Kandel?

Answer 10

Eric Kandel is an Austrian-American neuroscientist who received the nobel price in physiology or medicine in 2000 for his work on the plasticity of the Aplysia Californica.

Question 11

What is habituation?

Answer 11

Habituation is a process that causes an animal to become less responsibve to repeated occurences of a stimulus.

Question 12

Give an example of habituation in humans.

Answer 12

When dressing we initially experience tactile sensations due to clothes stimulating our skin, but habituation quickly causes these sensations to fade.

Question 13

What is sensitization?

Answer 13

Sensitization is a process that allows an animal to generalize an aversive response elicited by a noxious stimulus to a variety of other non-noxious stimuli.

Question 14

Give an example of sensitization in the Aplysia.

Answer 14

In Aplysia that have habituated to siphon touching, sensitization of gill withdrawal is elicited by pairing a strong electrical stimulus to the animal’s tail with another light touch of the siphon. This pairing causes the siphon stimulus to again elicit a strong withdrawal of the gill.

Question 15

In the Aplysia gill withdrawal reflex, what accounts for the habituation of the reflex?

Answer 15

During habituation, transmission at the glutamatergic synapse between the sensory and motor neurons is depressed. This depression is due to a reduction in the number of synaptic vesicles available for release.

Question 16

What accounts for the sensitization in the Aplysia?

Answer 16

The tail shock that evokes the sensitization activates sensory neurons that innervate the tail. These sensory neurons in turn excite modulatory interneurons that release serotonin onto the presynaptic terminals of the sensory neurons of the siphon. Serotonin enhances transmitter release from the siphon sensory neuron terminals, leading to increased synaptic excitation of the motor neurons.

Question 17

Short-term sensitization in the synaptic terminal of the Aplysia sensory neuron: Serotonin released by the facilitatory interneurons bind to ..

Answer 17

Serotonin released by the facilitatory interneurons bind to G-protein-coupled receptors on the presynaptic terminals of the siphon sensory neurons.

Question 18

Serotonin released by the facilitatory interneurons bind to G-protein-coupled receptors on the presynaptic terminals of the siphon sensory neurons. This does what?

Answer 18

Serotonin released by the facilitatory interneurons bind to G-protein-coupled receptors on the presynaptic terminals of the siphon sensory neurons. This stimulates the production of the second messenger, cAMP.

Question 19

Serotonin released by the facilitatory interneurons bind to G-protein-coupled receptors on the presynaptic terminals of the siphon sensory neurons. This stimulates the production of the second messenger, cAMP. What does cAMP do?

Answer 19

Serotonin released by the facilitatory interneurons bind to G-protein-coupled receptors on the presynaptic terminals of the siphon sensory neurons. This stimulates the production of the second messenger, cAMP. Cyclic AMP binds to the regulatory subunits of protein kinase A (PKA).

Question 20

Serotonin released by the facilitatory interneurons bind to G-protein-coupled receptors on the presynaptic terminals of the siphon sensory neurons. This stimulates the production of the second messenger, cAMP. Cyclic AMP binds to the regulatory subunits of protein kinase A (PKA). What happens to PKA?

Answer 20

Serotonin released by the facilitatory interneurons bind to G-protein-coupled receptors on the presynaptic terminals of the siphon sensory neurons. This stimulates the production of the second messenger, cAMP. Cyclic AMP binds to the regulatory subunits of protein kinase A (PKA). This liberates the catalytic subunits of PKA that are then able to phosphorylate several proteins, probably including K+ channels.

Question 21

Serotonin released by the facilitatory interneurons bind to G-protein-coupled receptors on the presynaptic terminals of the siphon sensory neurons. This stimulates the production of the second messenger, cAMP. Cyclic AMP binds to the regulatory subunits of protein kinase A (PKA). This liberates the catalytic subunits of PKA that are then able to phosphorylate several proteins, probably including K+ channels. How does this affect the presynaptic action potential?

Answer 21

Serotonin released by the facilitatory interneurons bind to G-protein-coupled receptors on the presynaptic terminals of the siphon sensory neurons. This stimulates the production of the second messenger, cAMP. Cyclic AMP binds to the regulatory subunits of protein kinase A (PKA). This liberates the catalytic subunits of PKA that are then able to phosphorylate several proteins, probably including K+ channels. The net effect of the action of PKA is to reduce the probability that the K+ channels open during a presynaptic action potential. This effect prolongs the presynaptic action potential, thereby opening more presynaptic Ca2+ channels.

Question 22

Serotonin released by the facilitatory interneurons bind to G-protein-coupled receptors on the presynaptic terminals of the siphon sensory neurons. This stimulates the production of the second messenger, cAMP. Cyclic AMP binds to the regulatory subunits of protein kinase A (PKA). This liberates the catalytic subunits of PKA that are then able to phosphorylate several proteins, probably including K+ channels. The net effect of the action of PKA is to reduce the probability that the K+ channels open during a presynaptic action potential. This effect prolongs the presynaptic action potential, thereby opening more presynaptic Ca2+ channels. Ca2+ channels are also probably enhanced by ..

Answer 22

Serotonin directly.

Question 23

Serotonin released by the facilitatory interneurons bind to G-protein-coupled receptors on the presynaptic terminals of the siphon sensory neurons. This stimulates the production of the second messenger, cAMP. Cyclic AMP binds to the regulatory subunits of protein kinase A (PKA). This liberates the catalytic subunits of PKA that are then able to phosphorylate several proteins, probably including K+ channels. The net effect of the action of PKA is to reduce the probability that the K+ channels open during a presynaptic action potential. This effect prolongs the presynaptic action potential, thereby opening more presynaptic Ca2+ channels. The enhanced influx of Ca2+ does what?

Answer 23

Serotonin released by the facilitatory interneurons bind to G-protein-coupled receptors on the presynaptic terminals of the siphon sensory neurons. This stimulates the production of the second messenger, cAMP. Cyclic AMP binds to the regulatory subunits of protein kinase A (PKA). This liberates the catalytic subunits of PKA that are then able to phosphorylate several proteins, probably including K+ channels. The net effect of the action of PKA is to reduce the probability that the K+ channels open during a presynaptic action potential. This effect prolongs the presynaptic action potential, thereby opening more presynaptic Ca2+ channels. Finally, the enhanced influx of Ca2+ into the presynaptic terminals increases the amount of transmitter released onto motor neurons during a sensory neuron action potential.

Question 24

Describe the mechanical differences between the short-term sensitization and the long-term sensitization in the Aplysia sensory neurons?

Answer 24

With repeated training (i.e. additional tail shocks), the serotonin-activated PKA involved in short-term sensitization now also phosphorylates - and thereby activates - the transcriptional activator CREB.

Question 25

With repeated training (i.e. additional tail shocks), the serotonin-activated PKA involved in short-term sensitization now also phosphorylates - and thereby activates - the transcriptional activator CREB. How does this cause long-term sensitization?

Answer 25

We don't know the mechanism exactly. We know that CREB binding to the cAMP responsive elements (CREs) in regulatory regions of nuclear DNA increases the rate of transcription of downstream genes.

Question 26

With repeated training (i.e. additional tail shocks), the serotonin-activated PKA involved in short-term sensitization now also phosphorylates - and thereby activates - the transcriptional activator CREB. What is the consequence of this on sensitization?

Answer 26

Two consequences: 1. CREB stimulates the synthesis of an enzyme, ubiquitin hydroxylase, that stimulates degradation of the regulatory subunit of PKA. This causes a persistent increase in the amount of free catalytic subunit, meaning that some PKA is persistently active and no longer requires serotonin to be activated. 2. CREB stimulates another transcriptional activator protein called C/EBP, whose mechanism is unknown, but is thought to be involved in the addition of synaptic terminals.

Question 27

Most of the work on LTP in humans has been from looking at a particular location in the human brain. Which?

Answer 27

The hippocampus.

Question 28

The hippocampus is often divided into three main areas. Which?

Answer 28

CA1, CA2, and CA3.

Question 29

The Hippocampus is often divided into three main areas: CA1, CA2, and CA3. What does "CA" refer to?

Answer 29

"CA" refers to cornu Ammonis, Latin for Ammon's horn - the ram's horn that resembles the shape of the hippocampus.

Question 30

LTP in the hippocampus: During low-frequency synaptic transmission, glutamate released by Schaffer collaterals bind to both NMDA-type and AMPA/kainate-type glutamate receptors. Why is the frequency relevant?

Answer 30

During low-frequency synaptic transmission, glutamate released by Schaffer collaterals bind to both NMDA-type and AMPA/kainate-type glutamate receptors. While both types of receptors bind glutamate, if the postsynaptic neuron is at its normal resting membrane potential, the pore of the NMDA receptor channel will be blocked by Mg2+ ions and no current will flow. Under such conditions, EPSP will be mediated entirely by the AMPA recetors. Because blockade of the NMDA receptor by Mg2+ is voltage-dependent, the function of the synapse changes markedly when the postsynaptic cell is depolarized. Thus, high-frequency stimulation will cause summation of EPSPs, leading to a prolonged deolarization that expels Mg2+ from the NMDA channel pore.

Question 31

How are the CA2+ entering through NMDA receptors relevant for LTP?

Answer 31

Several sorts of observations have confirmed that a rise in the concentration of CA2+ in the postsynaptic CA1 neuron - the result of CA2+ entering through NMDA receptors - serves as a second messenger signal that induces LTP.

Question 32

We don't fully understand the mechanism of LTP. How do we explain the strengthening of synaptic transmission during LTP?

Answer 32

It appears that the strengthening of synaptic transmission during LTP arises from an increase in the sensitivity of the postsynaptic cell to glutamate. Several recent observations indicate that excitatory synapses can dynamically regulate their postsynaptic glutamate receptors and can even add new AMPA receptors to synapses.

Question 33

What is the theoretical reasoning for the existence of LDP?

Answer 33

If synapses simply continued to increase in strength as a result of long-term potentiation, eventually they would reach some maximum efficacy, making it difficult to encode new information. Thus, to make synaptic strengthening useful, other processes must selectively weaken specific sets of synapses and LTD is such a process.

Question 34

There are many similarities between LTP and LTD at the Schafer collateral-CA1 synapses. Mention some similarities and some differences.

Answer 34

They both require activation of NMDA-type glutamate receptors, so that CA2+ flows into the postsynaptic cell. The major determinant of whether LTP or LTD arises appears to be the nature of the Ca2+ signal in the postsynaptic cell.

Question 35

The major determinant of whether LTP or LTD arises appears to be the nature of the Ca2+ signal in the postsynaptic cell. What differences are we talking about?

Answer 35

Small and slow rises in Ca2+ lead to depression, whereas large and fast increases in Ca2+ trigger potentiation.

Question 36

What do we know about the mechanism of LTD once Ca2+ enters through NMDA receptors?

Answer 36

We don't know anything for certain, but one line of evidence points to Ca2+-depended phosphatases that cleave phosphategroups from target molecules.

Question 37

What is spike-timing dependent plasticity (STDP)?

Answer 37

Spike-timing dependent plasticity is a not yet fully understood mechanism. STDP refers to the observed phenomenon where the timing is important for whether EPSP causes LTP or LTD. At a given (low) frequency of synaptic actibity, LTD will occur if presynaptic activity is preceded by a postsynaptic action potential, while LTD occurs if the postsynaptic action potential follows presynaptic activity.