Test 1 Part 1

Question 1

Define neuroplasticity

Answer 1

change that occurs in the brain that represents an enduring behaviour or cognitive change. This phenomenon occurs OUTSIDE OF NATURAL DEVELOPMENT.

Question 2

What are cell assemblies and how are their synapses strengthened

Answer 2

cell assemblies are PREEXISTING, MALLEABLE networks of cells that are connected together. Although they are preexisting, experiences can influence their synaptic strength through FACILITATION

Facilitation is characterized by events that allow for an increased efficiency in AP firing between a specific presyn and post syn cell, often through previous repeated excitation.

Question 3

What is facilitation

Answer 3

Facilitation is characterized by events that allow for an increased efficiency in AP firing between a specific presyn and post syn cell, often through previous repeated excitation.

Question 4

Short term facilitation is a transient process whose mechanism relies on:

Answer 4

ion channel modification on specific synapses that are firing together.

Question 5

Describe the molecular mechanism of short term facilitation

Answer 5

• In the case of the Aplysia tail shock reflex conditioning, the release of 5HT from a neuron when a tail shock is commenced results in 5HT binding to METABOTROPIC receptors on the sensory and motor neurons. In these neurons, a G protein is activated which commences a second messenger cascade, ultimately resulting in PKA activation via the creation of cAMP.
• PKA has the capacity to modify and open Ca2+ channels and close K+ channels through acts of phosphorylation. This influx of calcium results in the increase of membrane potential of the cell, effectively bringing it closer to threshold.
• Therefore, after the release of 5HT, the post synaptic cell is now more excitable and able to efficiently able to fire an action potential to a stimulus of the same intensity.
• This increase in membrane potential is only transient.

Question 6

Long term facilitation is a long lasting process that requires ____ _____ and results from ____ _____.

Answer 6

Long term facilitation is a long lasting process that requires protein synthesis and results from persistent experience.

Question 7

Describe the molecular mechanism of long term facilitation

Answer 7

Its intracellular events initially relies on the same processes as short term facilitation, where there is activation of PKA due to cAMP.

• PKA also phosphorylates MAPK, and both PKA and MAPK can enter the nucleus to activate (phosphorylate) CREB1: cAMP response binding protein, in addition to exerting its short-term effects.
• CREB1 TF is able to activate CRE promoter regions/genes, which can activate other genes that aid in synaptic growth and protein synthesis.
• The proteins synthesized (via translation) from the genes that were activated by CREB can be sent to the terminals of the presynaptic cell that was affected by serotonin originally binding (MARKED), representing recent CAPTURE activity. These proteins can then be used for further synaptic growth.

Question 8

in long term facilitation, what happens to the proteins that are made by CREB-activated genes?

Answer 8

The proteins synthesized (via translation) from the genes that were activated by CREB can be sent to the terminals of the presynaptic cell that was affected by serotonin originally binding (MARKED), representing recent CAPTURE activity. These proteins can then be used for further synaptic growth.

Question 9

In aplysia, how would you ensure that learning persists?

Answer 9

duration of learning is directly related to the nature of the experience. If you shock the aplysia repeatedly and frequently, there is a higher change that long term facilitation would occur and the learning would endure longer.

the duration of the memory is a function of the number of the repetitions of the noxious stimuli (how many trains over how many days)

Question 10

In the aplysia, the ___ motor neuron synapses with the gill so it can retract.

Answer 10

L7

Question 11

In terms of hebbian growth and neuroplasticity, how does learning result?

Answer 11

from chnages in the strength of the synaptic connections between precisely interconnected cells.

Question 12

which neurotransmitter modculates the gill withdrawal reflex

Answer 12

5HT

Question 13

In order to induce learning, why do we need persistent action?

Answer 13

because we have a bunch of mechanisms in place that actively restrict the entire synaptic growth process LIKE PHOSPHOTASES. Therefore, we need more persistent activation to override this.

Question 14

Long term facilitation occurs through nuclear events rather than at the synapse like short term facilitation. How do we ensure that nuclear events do not affect all the synpases that the cell has contacts with? How do you ensure synaptic specificity?

Answer 14

Puffs of 5HT can send a signal to the nucleus of a neuron to activate CREB, which then appears to send proteins to ALL terminals. However, only those terminals that have been marked by 5HT previously could use the proteins for synaptic growth.

therefore, short term facilitation has 2 functions: 1) short term memory storage
2) locally marks the specific synapse for subsequent capture of proteins necessary for long term facilitation and growht when more 5HT is applied to another set of terminals.

therefore, if there is a persistent stimulus somewhere else, a brief pulse of 5HT at another location produces another change (TAGGING). The 5 5ht Pulse can modify the clel body, which can exert effects onto its other synapses. Priming the other synapse with 1 small 5HT allows for proper mRNA expression and allows the other neuron to respond to later neuronal stimuli.

ONLY the synapses that have been tagged by either the large dose of 5HT or the small primind dose of 5HT will be modified long term. the synapses that are not will be left alone.

Question 15

Where does LTP occur in the hippocampus?

Answer 15

the perforant path of HC demonstrates activity-dependent pathway.

Question 16

Short term potentiation in the HC is facilitated by

Answer 16

activation of a post syn neuron via NMDA receptor can result in an enhances response to an input.

Question 17

Outline the mechanism behind short term potentiation

Answer 17

DA is a modulator the way 5HT in the aplysia was before.
Activation of a synapse through electrical stimulation causes glutamate release. This glu activates AMPA receptors, then NMDA receptors, resulting in Ca2+ influx.

If there is too much Ca2+, phosphatase calcineurin is activated, resulting in the deactivation of various proteins, including PKA, preventing LTP. This is where Da comes in.

DA inihibits phosphatases, which are normally activated by Ca2+, so that Ca2+ persists with no downregulation, allowing for long term changes because PKA can now be persistently activated.

ALSO: NMDA receptors can cause Ca2+ increase, which also causes calmodulin activation, then increased cAMP, increased PKA, then CREB activation, then STRUCTURAL CHANGES VIA BDNF EXPRESSIOn.

Question 18

explain how PKA is involved with fear conditioning experience

Answer 18

disrupting PKA activity via mutation (inability to entre nucleus) blocks long term learning (they cannot learn the sound-shock association for over a day), but does not prevent short term learning. Blocking protein synthesis with anisomycin also prevents long term potentiation in PKA normal mice.

Question 19

QUESTION ON TEST: provide three experimental results that demonstrate the role of PKA in reward-related learning

Answer 19

PKA Has a Role in Reward-Related Learning:
- PKA is involved in LEARNING ACQUISITION, NOT FOR RETAINING/RECOLLECTION.
- Proof:
o Approach training: If you put rpCAMPS (PKA inhibitor) into the NAcc, BLA or mPFC of rats prior to training, approach response will not be learnt. BUT: administering RpCAMPS after training had no effect on the performance.

o Lever pressing: administering RpCAMPS into NAcc or mPFC of rats prior to lever press conditioning prevented the acquisition of the lever press response, but administering it after conditioning allowed them to STILL CONTINUE TO HAVE A RESPONSE (NO CHANGE IN PERFORMANCE)

o Administration of a PKA activator (CTX) into the NAcc prior to lever press training PREVENTED THE ACQUISITION of the lever press response, but applpying CTX later did not affect the lever press reponse.
Indicates that there is an OPTIMAL LEVEL OF PKA, NOT TOO LITTLE AND NOT TOO MUCH

Question 20

QUESTION ON TEST: Describe how dopamine and glutamate interact in the nucleus accumbens to produce synaptic alterations

Answer 20

Synaptic alterations occur in the nucleus accumbens through the COINCIDENT ACTIVATION of cortical (environmental) glutaminergic neurons, and VTA (rewarding) dopaminergic stimuli which interact at the nucleus accumbens- GABAergic motor neuron efferents.

This synaptic-strengthening process allow for the conditioning of an environmental stimulus to PREDICT a rewarding stimulus, BUT NEITHER NT ALONE COULD RESULT IN SYNAPTIC ALTERATIONS.

Glutamate release from cortical neurons stimulates NMDA receptors to increase CA2+, which facilitates adenylyl cyclase coupling to D1 receptors in the NAcc. At the same time, when a food/reward is given just after the environmental stimulus, DA release from VTA into the NAcc activates the D1 receptors, which are highly coupled to the adenylyl cyclase.
- This results in a lot of adenylyl cyclase activation. AC activates PKA (and MAPK) which activates CREB TF which can facilitate protein synthesis through gene transcription.
- PKA also activates DARP22, which inhibits any phosphatases that could potentially deactivate any of the newly phosphorylated proteins.
- These synthesized proteins (due to CREB) create new glutamate receptors so that the neurons in the NAcc are more responsive to glutaminergic environmental stimuli.
o THERE IS AN ENHANCED SIGNALLING IN THE Nacc-Motor neurons synapse via upregulation of Glu receptors.
o Therefore:
♣ DA modifies the strength of Glu cortical inputs into the NAcc, but only if the Glu synapses were recently activated by environmental stimuli, causing a coupling of adenylyl cyclase to D1 receptors. After this strengthening occurs, the Glu synapses can now influence motor responses even in the absence of DA.