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Cellular Basis Of Learning And Memory > Lectures 9 & 11 > Flashcards

Lectures 9 & 11 Flashcards

1
Q

What does Long-Lasting LTP depend on?

A

Translation and Transcription (locally and genomically)

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2
Q

Are there multiple signaling pathways from an LTP signaling event or just one?

A

Many

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3
Q

What happens if you block any of the signaling cascades from an LTP signaling event?

A

Memory will be affected somehow

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4
Q

What is the goal of synapse to nucleus signaling pathways? (Think a particular protein)

A

Phosphorylation of CREB which leads to transcription

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5
Q

What are the three main sources of synapse to nucleus signaling?

A
  • G-protein coupled receptors
  • NMDA mediated Ca2+ influx
  • BDNF-Trk B signaling cascade
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6
Q

What is BDNF important for when it comes to synapses?

A

Synaptic plasticity

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7
Q

How many waves of protein synthesis are there during an LTP event?

A

Two waves

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8
Q

What mediates the two waves of protein synthesis?

A

Calcium stores

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9
Q

Where does the first wave of protein synthesis occur?

A

In the dendrites

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10
Q

Describe the second wave of protein synthesis

A

It occurs when protein is synthesized from the new mRNA produced by the genomic signaling cascade

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11
Q

What is the initial and second messenger that begins the signaling cascade?

A

Ca2+ is both

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12
Q

What are the two places that source the calcium necessary for protein translation?

A

Extracellular (fluid) and intracellular (ER)

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13
Q

What are the two extracellular source of calcium and how are they different?

A
  • NMDAR: often source for smaller stimulations and enters through dendritic spines
  • vdCC: often source for LARGER stimulations and enters through the soma
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14
Q

What are the two sources of calcium from the intracellular ER and how do they differ?

A
  • RyRs: stores Ca2+ when it binds to it in the spine
  • IP3R: stores Ca2+ when IP3 binds to IP3Rs in the dendrite
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15
Q

What are the three compartments of a neuron?

A
  • spine compartment
  • dendritic compartment
  • soma compartment
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16
Q

What are the two mechanisms Metabotropic receptors use to influence postsynaptic response to stimulation?

A
  • alter the opening of a G-protein-gated ion channel
  • stimulate an effector enzyme that either synthesizes or breaks down a second messenger
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17
Q

What do IP3Rs respond to?

A

Ca2+ and IP3

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18
Q

When is IP3 synthesized?

A

When glutamate binds to mGluR1

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19
Q

What are the 3 forms of LTP?

A

LTP1, LTP2, and LTP3

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20
Q

How is LTP1 induced?

A

Glutamate produced by a weak stim binds to NMDA which leads to an influx of Ca2+ into the spine.

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21
Q

What does LTP1 cause?

A

Ca2+ influx from the spine binds to the RyRs and causes the ER to release additional Ca2+ into the spine

22
Q

What induces LTP2?

A

Glutamate from a strong stim binding to NMDA and to the mGluR1s

23
Q

What does LTP2 cause?

A

Local protein synthesis

24
Q

What produces LTP3?

A

Strong stimulation opens the vdCCs and Ca2+ in the soma increases to the point it can translocate to the nucleus

25
Q

What does LTP3 cause?

A

Ca2+ in the soma translocates to the nucleus and initiatives transcription of genes necessary for the expression of LTP3

26
Q

What problems does local protein synthesis solve?

A
  • specificity to the spine level
  • it creates a protein on demand system
27
Q

How do mRNAs arrive at specific dendritic locations?

A

RNA binding proteins attach them to cytoskeleton motor proteins

28
Q

Once transported to the dendritic spine region, what does mRNA do?

A

The mRNA cycles between nearby spines

29
Q

What uncages glutamate?

A

Photon stimulation

30
Q

What does uncaging glutamate do?

A

There is rapid changes in the spatial distribution of mRNA & polyribosome complexes form to translate mRNA into new protein that is captured by the spines

31
Q

What are some of the proteins that will be synthesized from the mRNA from local protein synthesis?

A

PSD-95, Arc, GluA1, CaMKII, AMPA, more

32
Q

What is required to assemble Ribosomal Complexes?

A

Basic Ribosomal Unit/mRNAs known as TOPS

33
Q

What are TOPS in regards to translation?

A

Translation factors

34
Q

What does translation of TOPS depend on?

A

Activity dependent

35
Q

What does BDNF bind to?

A

TrkB

36
Q

What are TrkB receptors colocalized with?

A

NMDA and AMPA

37
Q

What does BDNF binding to TrkB do?

A

Activates complex kinase mTOR (mammalian target of rapamycin)

38
Q

What does mTOR do?

A

Inhibits TOP protein 4E-BP

39
Q

What does 4E-BP do?

A

Block translation of other TOPS such as EFs (Elongation factors) & IFs (initiation factors)

40
Q

What does the inhibition of 4E-BP allow small ribosomal units to do?

A

Combine with other TOPS like EFs and IFs to form functional polyribosomal complexes to translate mRNA

41
Q

What happens to LTP if a TrkB inhibitor is introduced shortly after induction?

A

LTP can be generated but it cannot endure

42
Q

What happens to LTP if you introduce a TrkB inhibitor at 80 minutes after induction?

A

No effect

43
Q

What is TrkB activity required for?

A

Local protein synthesis and it is required in less than 80 minutes

44
Q

What are the two things the consolidation of memory is involved in?

A

Degradation of existing proteins and protein synthesis

45
Q

How are proteins that regulate/suppress translation dealt with to allow for synaptic plasticity? What activates what?

A

Ubiquitin Proteasome Systems are activated by glutamate and CaMKII recruits proteasome molecules to the spines

46
Q

What is Arc?

A

A protein derived from the immediate early gene Arc

Arc stands for activity regulated cytoskeleton-associated protein

47
Q

What is the antisense technique?

A

A technique that prevents translation of specific proteins by introduced a synthesized strand of nucleic acid that will bind to specific mRNAs

48
Q

What is Arcs role in the consolidation of LTP? (Less the actual function and more so how long until its removal has an effect)

A

Arc antisense at 160 minutes after induction reverses LTP, but not after 280 minutes

Therefore, after 280 minutes synaptic changes have been consolidated

49
Q

What are the current thoughts on what Arc does and why do we think that?

A

Arc may regulate the regulation of Actin dynamics by phosphorylating cofilin for several hours, this is based on Arc absence leading to large reductions in phosphorylated cofilin and a corresponding loss of new actin filaments

50
Q

What does memory reflect?

A

The changes in synaptic connections within the neuronal ensemble, activated by the experience

51
Q

What is important to retrieving a memory?

A

Presynaptic neuron depolarizing downstream neurons sufficiently to produce APs that will activate the whole engram (something that cant be done by a changing synaptic strength in a single spine)

52
Q

What is the Clustered Plasticity Model?

A

The idea that the dendritic branch becomes the fundamental storage unit when we think of memory. The clustered potentiated synapses are more effective than distributed ones and they can share new proteins among the spines

Cellular Basis Of Learning And Memory (7 decks)

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