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Neurobiology of Learning & Memory > Exam 2: Chapter 3-8 > Flashcards

Exam 2: Chapter 3-8 Flashcards

1
Q

What is the goal of the generation phase of LTP?

A

Inserting GluA1 receptors into the post-synaptic density

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2
Q

Generation of LTP

What is the role of Ionotropic glutamate receptors and where are they found?

A

Ionotropic receptors are located in the plasma membrane in dendritic spines on the PSD. When Glu binds to the receptor, the channel opens and allows ions (such as Na+ or Ca2+) to enter the cell.

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3
Q

Generation of LTP

What is an NMDA antagonist?

A

APV

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4
Q

Generation of LTP

What is an AMPA receptor antagonist?

A

CNQX

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5
Q

Generation of LTP

What receptors are required for generation of an LTP and when?

Induction vs. expression

A
  1. AMPA is required for both induction & expression of LTP
  2. NMDA is only required for induction of LTP
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6
Q

What were Collingridge’s results that established the importance of NMDA receptors to our understanding of LTP?

A

He found that inhibiting NMDA receptors prevented the induction of LTP but did not influence its expression.

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7
Q

Generation of LTP

What are the 2 events that open the NMDA channel?

A
  1. Glu binds to the both AMPA & NMDA receptors
  2. Na+ entering the cell must depolarize it in order to remove the Mg2+ plug allowing Ca2+ to enter the cell.
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8
Q

Generation of LTP

What were Gary Lynch’s 2 complimentary ideas?

A
  1. An LTP-inducing stimulus can rapidly incr. the number of AMPA receptors in the dendritic spine
  2. This is the fundamental outcome that supports the expression of LTP
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9
Q

Generation of LTP

How are AMPA receptors moved?

A

AMPA receptors traffic into and out of dendritic spine regulated constitutively by synaptic activity.

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10
Q

Generation of LTP

What is stargazin?

What are its structural features?

A

Stargazin is a transmembrane AMPAr regulatroy protein (TARP) that co-assembles with AMPA receptors.

  • Terminal end binds to membrane
  • Has serine site for phosphorylation
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11
Q

Generation of LTP

Describe the constitutive process of AMPA trafficking.

A
  • AMPA receptors are in constant random motion laterally diffusing along the plasma membrane.
  • Receptors may be caught in the endocytotic zone and packaged for recycling.
  • Endosomes (intracellular vesicles containing AMPA receptors) deliver the receptors to the peri-synaptic region near the PSD.
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12
Q

Generation of LTP

How does protein kinase A (PKA) affect GluA1?

A

PKA phosphorylates the AMPAr to traffic the endosomed receptor to the peri-synaptic region.

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13
Q

Generation of LTP

How does protein kinase C (PKC) affect GluA1?

What is PKC activated by?

A

PKC, activated by Ca2+ (synaptic activity), phosphorylates the receptor and helps localize it to the PSD.

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14
Q

Generation of LTP

How does CaMKII affect GluA1?

A

CaMKII phosphorylates the receptor and changes the GluA1 channel to allow influx of Ca2+ and Na+.

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15
Q

Generation of LTP

Describe the process of lateral diffusion increasing the AMPA receptors in the PSD.

A
  1. Influx of calcium into the spine via NMDA receptors
  2. Activates CaMKII
  3. CaMKII phosphorylates serine residues on the terminal of Stargazin
  4. Release of Stargazin terminals from membrane
  5. Binding of Stargazin terminals to PSD-95 complexes, thereby trapping the receptor in the PSD
  6. The stability of Stargazin incr as CaMKII phosphorylates more residues
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16
Q

Generation of LTP

How is Ca2+-Calmodulin built?

Why is Calmodulin considered a surrogate second messenger?

A

Calmodulin undergoes a conformational change when it binds to Calcium. The new shape enables it to bind to other proteins that do no have Ca2+ binding sites.

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17
Q

Generation of LTP

Describe the structure of CaMKII?

Describe each domain. How is it activated?

A

The CaMKII subunit consists of 2 domains: an autoinhibitory domain and catalytic domain.

The regulatory domain contains a phosphorylation site (Thr286) that is not accessible when the kinase is in an inactive state. Ca2+ + calmodulin serves as a second messenger and activates the kinase to expose the catalytic domain and Thr286

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18
Q

Generation of LTP

How does CaMKII autophosphorylate?

A

Subunits of the kinase assemble into a ring-like structure called a holoenzyme. A subunit can now phosphorylate its neighbor.

This process of autophosphorylation enables the subunits to remain active even when Ca2+ + calmodulin is no longer present.

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19
Q

Generation of LTP

What is the second, but slower way to deliver AMPA receptors to the PSD?

A
  1. Neuronal activation leads to an influx of Ca2+
  2. Incr Ca2+ induces a conformation change in the motor protein, myosin Vb
  3. The unfolding of myosin Vb mediates the recruitment of the motor to the membrane-associated Rab11 effector complex on the recycling endosome
  4. The activated myosin then delivers AMPA receptors to synaptic sites
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20
Q

Generation of LTP

What are the 2 pools of AMPA receptors to the PSD?

What are there roles?

A
  1. Preexsisting Surface Pool (Lateral Diffusion Pool): important for rapid generation of LTP
  2. Intracellular Pool (Endosomed Pool): sustains a slower incr. in LTP
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21
Q

Generation of LTP

What happens if lateral diffusion is inhibited?

A

If lateral diffusion is inhibited, then the intial delivery of AMPA receptors is prevented and the rapid generation of LTP does not occur.

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22
Q

Generation of LTP

What happens if exocytosis is inhibited?

A

Inhibiting the delivery of the intracellular pool results in the rapid reduction of LTP, which returns to baseline in about 10 min.

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23
Q

Generation of LTP

What is actin?

What is its role in the generation of LTP?

A

Actin is a cytoskeleton protein that determines the architecture of neurons, including dendritic spines.

The rapid insertion of AMPA receptors to the PSD requires disassembling the actin networks.

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24
Q

Generation of LTP

What are the 2 states actin is found in?

A
  1. Monomer state (G-actin)
  2. Polymer state (F-actin)
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25
Q

Generation of LTP

How are actin networks disassembled in the calpain-spectrin pathway?

A
  1. Filament actin in the spine head is crosslinked with spectrins
  2. The protease calpain is activated when Ca2+ enters the spine
  3. Calpain degrades spectrins and facilitates the disassembling of actin
  4. This activity contributes to the rapid insertion of additional AMPA receptors in the PSD
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26
Q

Generation of LTP

Summarize the Generation Phase.

A
  1. LTP is generated within about a minute following the induction stimulus.
  2. Following the entry of Calcium, the actin cytoskeleton is degraded by a calpain-spectrin pathway
  3. AMPA receptor lateral diffusion trafficking processes rapidly insert and trap GluA1 receptors into PSD
  4. AMPA receptors within recyling endosomes are mobilized to the PSD via a Ca2+ conformational change on myosin Vb
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27
Q

Stabalization of LTP

When LTP returns to baseline, it is most likely a result of what?

A

Constitutive endocytotic processes want to remove AMPA receptors from the PSD

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28
Q

Stabalization of LTP

What produces bigger spine sizes that are more stable?

A

Theta burst stimulation that produces LTP increases spine size.

Larger spines have increased AMPAr

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29
Q

Stabalization of LTP

Describe the 3 stages of the stabalization phase?

A
  1. Long peices of actin cytoskeleton are cut up into smaller peices
  2. Use the samll peices of actin cytoskeleton to repolymerize into bigger peices
  3. Defend the bigger spine that was just created
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30
Q

Stabalization of LTP

What regulates actin polymerizatoin?

What are the active and inactive states?

A

Cofilin regulates actin polymerization.

In its normal unphosphorylated state, cofilin severs and depolymerizes actin filaments.
When phosphorylated, cofilin no longer interfers with actin polymerization.

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31
Q

What are the states of actin in both generation of LTP and stabalization.

A

Generation = actin depolymerization
Stabalization = actin polymerization

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32
Q

Stabalization of LTP

How do drugs that prevent actin polymerization applied before TBS affect LTP?

A

They do not prevent the induction of LTP, but it will rapidly decay.

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33
Q

Stabalization of LTP

What are the processes invovled in stabalization of LTP?

The disassembling step

A
  1. CAMKII detaches from F-actin strands & unbundles actin
  2. Unbundled actin is exposed to cofilin that helps depolymerize actin
  3. Actin binds to actin-interacting proteins that cap the fragments to prevent rejoining
  4. Myosin IIb shearing of long to short polymerized actin
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34
Q

Stabalization of LTP

What is the role of Myosin IIb?

How do drugs that inhibt myosin IIb affect LTP?

A

Myosin IIb exerts a shearing action that breaks actin filament into smaller units that can be re-assembled elsewhere in the spine.

Applying drugs that inhibit myosin IIb prior to TBS prevents the stabalization of LTP but does not interfere with its induction.

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35
Q

Stabalization of LTP

In an unpotentiated spine what is the intial state of the actin cytoskeleton?

A

Actin filaments are connected in a meshlike network in the spine head. Strands of neck actin filaments are bundled by* inactive CaMKII* complexes

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36
Q

Stabalization of LTP

What happens to the CaMKII bundling the actin filaments when an inducing stimulus is applied?

A

An LTP-inducing stimulus opens NMDA receptors and calcium enters the spine. CaMKII is actviated. CaMKII disengages from the actin filaments and unbundles them.

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37
Q

Stabalization of LTP

How is the depolymerization of actin turned off?

A
  1. Cofilin is phosphorylated by LIMK halting the severing process
  2. Phosphatases dephosphorylate actin
  3. Allows rapid polymerization of long actin strands that promotes spine extension.
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38
Q

Stabalization of LTP

How is the dendritic spine elongated during stabalization?

A
  1. Profilin enters the spine to promote polymerization
  2. Arp2/3 promotes actin branching & expansion of the spine head
  3. Alpha-actinin promotes crosslinking fibers
  4. Inactive CaMKII promotes actin bundling
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39
Q

Stabalization of LTP

Describe uncaging glutamate.

A

You can tag glutamate with a really heavy moleucle so that it is to big to move and function. A specific directed UV light breaks the bond to free glutamate. Once uncaged the glutamate binds to AMPA and NMDA receptors and leads to massive restructuring of the cell.

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40
Q

Stabalization of LTP

What are the 2 pathways that regulate polymerization and reorganization?

What are they activated by?

A

Calcium entering the synapse through NMDA receptors activates the GTPases Rho-Rock & Rac-PAK. These enymes phosphorylate LIMK, a kinase that allows cofilin to allow actin polymerization.

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41
Q

Stabalization of LTP

What are cell adhesion molecules?

What are the 2 classes?

A

Proteins that are located on the cell surface and bind with other cells or with the extracellular matrix. Activated by synaptic activity.

  1. Neural Cadherins
  2. Integrin receptors
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42
Q

Stabalization of LTP

How do neural cadherins stabalize the synapse?

A

N-cadherins are reorganized by an LTP-inducing stimulus. Cadherin dimerization so the now-endlarged spine containing additional AMPA receptors is tightly coupled to the presynaptic terminal and well positioned to recieve glutamate.

Spines activated by TBS become larger and contain clusters of N-cadherins anchored to F-actin.

43
Q

Stabalization of LTP

How do integrin receptors contribute to stabalization of LTP?

How does this affect resistance to depolymerization?

A
  1. Calcium enters the spine from GluA1 due to CAMKII phosphorylation affecting conductance
  2. Incr. calcium levels traffic integrin receptors in the PSD region, where they bind to ligands in the extracellular matrix.
  3. As a result of activation of integrin receptors, actin filamentsand spectrins increase their resistence to depolymerization.
44
Q

Consolidation of LTP

What is the consolidation hypothesis?

What is cellular consolidation?

A

New memories require a long period of time to consolidate and become resistant to disruption. Cellular consolidation is a different phase of LTP beyond intial enlargenening of the action cytoskeleton, involing the transcription and translation of new proteins.

45
Q

Consolidation of LTP

What is the De Novo signaling hypothesis?

What experiment proved this hypothesis?

A

The idea that new proteins need to be formed for an enduring LTP.

Adding anisomycin, a protein synthesis inhibitor, prevents long lasting LTP

46
Q

Consolidation of LTP

What are the 2 pathways that support L-LTP?

A

Local translation (exisisting transcripts) and genomic signaling (transcribe new mRNA)

47
Q

Consolidation of LTP

What are plasticity products?

What generates them?

A

Plasticity products are new mRNA and protein generated as a result of synpatic activity. Phosphorylation of transcription factor CREB generates plasticity products.

48
Q

Consolidation of LTP

What is local protein synthesis?

A

mRNA and protein translation machinery, such as the ER and ribosomes, are present locally in the dendritic spine region. Synaptic activity intiates second messenger-kinase activity that results in translation of a new protein.

49
Q

Consolidation of LTP

What is the evidence for local protein synthesis through isolation of dendrites?

A

Seperating the dendrite from the soma prevents the delivery to the stimulated synapses of new proteins that were the product of a genomic signaling cascade. However stimulation to the Schaffer collateral fibers can still produce a L-LTP.

50
Q

Consolidation of LTP

What is the evidence for local protein synthesis through the Bradshaw experiment?

A

Placing Emetine, to block protein synthesis, in the distal dendrites prevents L-LTP because L-LTP depends on local dendritic translation.

51
Q

Consolidation of LTP

Describe the synapse-to-nucleus signaling molecule of genomic signaling.

A

Synaptic activity intitates a cascade that produces signaling moelcules (kinases) that eventually translocate to the nucleus to intiate transcription of CREB that target genes needed for enduring LTP.

Ex: waiter (kinase) taking order to the kitchen (nucleus)

52
Q

Consolidation of LTP

Describe the soma-to-nucleus signaling model of genomic signaling.

A

As a result of action potentials produced by synaptic activity, Ca2+ enters the soma through voltage-dependent calcium channels where it can more directly intiate transcription by activating kinases to phosphorylate CREB that target genes needed to consolidate LTP.

Ex: influx of ingredients (plasticity products), toward dendrite

53
Q

Provide experimental support for the soma-to-nucleus model.

A

S-LTP can be converted into L-LTP by initiating action potentials without strongly stimulating synapses. CA1 neurons are weakly stimulated and then action potentials are initiated in the same CA1 cells. These action potentials alone also were sufficient to phosphorylate CREB protein.

54
Q

What is the major assumption in the soma-to-nucleus signaling model?

A

Action potentials produced when a cell depolarizes open voltage dependent calcium channels near the soma that signal the nucleus.

55
Q

Consolidation of LTP

What are the 2 waves of LTP protein synthesis?

A
  1. The first wave occurs locally in dendrites.
  2. The second wave occurs when new protein is synthesized from the new mRNA produced by the geonomic signaling cascade.
56
Q

Consolidation of LTP

What are the extracellular sources of Calcium?

How can extracellular Ca2+ enter the neuron?

A

Ca2+ is present in the extracellular fluid and can enter a dendritic spine through NMDA receptros and can enter the soma through vgCCs.

57
Q

Consolidation of LTP

What are the intracellular source of Calcium?

How can intracellular Ca2+ move within the neuron?

A

Ca2+ is present intracellularly in the ER and can be released into spines with bound to RyRs located in spines or released into dendrites when IP3 binds to IP3rs in the dendrites.

58
Q

Consolidation of LTP

What is calcium induced calcium release (CICR)?

What does it contribute to?

A

When calcium enters through NMDA receptors it binds to ryanodine receptors and release intracellular Ca2+ stored in the ER located in the dendritic spine compartment.

May contribute to some of the post-translation effects to induce LTP, but won’t contribute to consolidaiton.

59
Q

Consolidation of LTP

How do IP3 receptors contribute to consolidation?

A

IP3 receptors release calcium through the dendritic compartment when activated by the second messenger IP3.

60
Q

Consolidation of LTP

What does mGluR1 do?

A

Activation of mGluR accumaltes IP3, but it does not allow the conductance of anything.

61
Q

Consolidtion of LTP

How do multiple sources of calcium contribute to LTP?

A

The more Ca2+ sources engaged, the more transcription and translation processes that increase stability and consolidation of synaptic changes that support LTP.

62
Q

Consolidtion of LTP

How does mRNA arrive at local dendrites?

A

To arrive at specific dendritic locations, mRNAs depend on RNA-binding proteins which bind to elements within the mRNA and attach those elements to cytoskeleton motor proteins.

63
Q

Consolidtion of LTP

Describe the mobility phases of mRNA.

Stationary vs. Mobile - What changes their location?

A

mRNAs have a stationary phase and mobile phase cycle. Their location can be changed by synaptic activity and resulting changes to specific spines.

64
Q

Consolidtion of LTP

What are polyribosome complexes?

A

Functional ribosomes form polyribosome complexes that translate mRNA into new protein that is capured by stimulated spines.

Polyribosomes are really good at translating new proteins

65
Q

Consolidtion of LTP

How are the mRNAs captured?

What does it depend on?

A

Spines stimulated by glutamate enlarge and capture mRNA and ribosomes. To capture mRNAs and ribosomes, the actin cytoskeleton must be polymerized.

Capturing of transcripts soley depends on post-translational modifications, not new protein synthesis.

66
Q

Consolidtion of LTP

What is a TOP mRNA?

A

TOP mRNAs encode initiation factors and elongation factors that are part of the translation machinery. TOP mRNA translation allows their joining of polyribosomal complexes that can translate other proteins.

Part of the endocytosed transcripts that are rotating near dendritic spines.

67
Q

Translating TOPmRNAs has a diff cascade intiated by synaptic activity

Describe the BDNF + Glu. pathway.

A

Local protein synthesis begins when BDNF binds to TrkB receptros that are colocalized with NMDA and AMPA receptors. This leads to activation of a complex kinase called mTOR that removes the repressing influence of the TOP protein 4E-Bp, so that small ribosomal subunits can combine with other TOPs to produce functional polyribosomal complexes that translate mRNA into protein.

68
Q

What happens when you interefere with TrkB function?

shortly after induction vs. 80 min after induction, What does this show?

A
  • Interfereing with TrkB function shortly after induction of LTP has no effect on the generation, but prevents LTP from enduring
  • Interfering with Trk B function 80 min after induction has no effect on either the generation or endurance of LTP

This shows that TrkB activity is required to intitate local protein synthesis.

69
Q

Application of rapamycin blocks mTOR kinase.

What happens when mTOR kinase is inhibited?

What does this show?

A

Inhibition of mTOR kinase prevents the late-phase LTP.

This shows that mTOR activity is required to intiate local protein synthesis.

70
Q

Describe the post-translational modification ubiquitination.

A

A polyubiquitin chain marks the protein for delivery to the proteasome and protein degradation.

71
Q

What happens when you inhibit the proteasome?

Prior to induction vs. after induction

A
  • inhibiting the proteasome function prior to inudction enhances the early phases of LTP, but prevents LTP from enduring
  • inhibiting the proteasome function 120 min after induction does not prevent LTP from enduring
72
Q

The enhacned LTP by proteasome inhibition is blocked by inhibitng mTOR

How does mTOR activity interact with the UPS system?

A

The activation of mTOR pathway is responsible for the initial enhancment of LTP that was unmasked by interfering with the UPS function

73
Q

Why does inhibiting the UPS intitially enhance LTP?

A

Local protein synthesis resulting from activating the BDNF-TrkB-mTOR pathway must be tightly regulated so that synaptic proteins are not overproduced. The UPS ensures this is the case by limiting the expression of translation activators.

74
Q

Why does inhibiting proteasome function prevent LTP from enduring?

A

During UPS inhibition, 4E-BP and other translational repressor proteins accumulate so that the local translation of mRNAs needed to sustain LTP is prevented and LTP decays down to baseline.

75
Q

What is the Arc protein?

Activity Related Cytoskeleton Associated Protein (Arc)

A
  • Arc protein is an immediate early gene: a gene that is transcribed rapidly in response to strong synaptic activity because its transcription does not require the prior translation of some other protein
76
Q

Describe Arc mRNA.

A
  • Arc mRNA is quickly transported precisely to the regions of synaptic activity that intiated the transcription signal
  • Arc mRNA becomes available in local regions at the time the local translation machinery is enhanced
77
Q

How does Arc sustain actin polymerization?

What happens to actin when you inhibit Arc synthesis?

A

When Arc synthesis is prevented there is a large reduction in phosphorylated cofilin, a corresponding large loss of new actin filaments. This means that Arc contibutes to the consolidation of LTP by sustaining actin polymerization.

78
Q

What is the clustered plasticity model?

What is the foundation for this model?

A

The clustered spines on a dendritic branch, rather than individual spines, is a fundamental storage unit

Fewer synaptic inputs are required to intiate an action potential when clusters of snyapses are stimulated on a few dendrites than when they are distributed on multiple dendritic branches.

79
Q

What is the sharing protein aspect of the clustered plasticity model?

A

When spines are stimulated, they not only attract mRNA and ribosomes for translation; the new proteins can be shared amond nearby spines so that a cluster of modified spines is created.

80
Q

Describe the evidence for protein sharing among dendritic spines.

A

When you have a strong uncaging and a weak uncaging in a clustered spine, the spine with the strong uncaging can produce local protein synthesis and share it with the weak uncaging spine so that both synapses become enlarged.

81
Q

What are the sources of BDNF?

A

BDNF released from presynaptic neurons binds to TrkB receptors, found in the PSD, causing the additional release of BNDF from the postsynaptic cell. This results in a positive feedback loop that helps sustain BDNF in the local extracellular region.

82
Q

What are three assumptions in regards to the synaptic tag hypothesis?

A
  1. Weak stimulation only tags synapses
  2. Strong stimulation tages synapses and genereated plasticity products
  3. Both tags and plasticity products are transient
83
Q

What are the 2 general effects of synaptic activity potentiating synapses?

A
  1. It can generate a synaptic tag, which will allow the stimulated spine to subsequently capture newly transcribed plasticity molecules
  2. It can engage the translation and transcription machinery to generate new plasticity products
84
Q

What is the evidence that shows that weakly tagged synapse capture plasticity products generated by strongly stimulated synpases?

A

A weak stimulus that normally would produce a short-lasting LTP will produce a long-lasting LTP if a strong stimulus is delivered to synapses belonging to the same neuron. This happens because the synaptic tags produced by the weak stimulus will capture plasticity products genreated by the strong stimulus.

85
Q

What is structurally different about a tagged synapse?

What effect does the structure have?

A

Tagged spines have a posttranslationally-dereived enlarged actin cytoskeleton. The enlarged actin cytoskeleton induces the invasion of microtubules into the spine where they can deliver mRNAs for translation.

86
Q

What is an inverse tag?

A

Arc accumulates on inactive CaMKII where it particpates in removing AMPA receptors. Arc-inactive CAMKII is an inverse tag.

87
Q

What is the molecular turnover problem?

A

The synaptic molecules that support memory traces are short-lived in comparison to the furation of our memories.

88
Q

What are the 2 forces that left unchecked operate to return synapses to their unpotentiated state?

A
  1. Molecular degradation
  2. Consititutive, endocytic processes that operate to cycle AMPA receptors out of the synaptic region
89
Q

Describe the erasure criteria.

A

A “memory molecule” should not be required to generate and initially stabalize/consolidate LTP but should be required for the duration of the LTP. Interefering with the activity of that molecule at any time following the protein-synthesis phase should return the strenghtend synapses to their baseline state.

The inhibitor should not alter basic neurnal transmission

90
Q

What speical properties does PKMz have that would make it a promising memory maintenance molecule?

A
  1. No inhibitory subunit / does not need second messenger
  2. mRNA is present in dendrites
  3. Self perpetuates
91
Q

Describe the ways the PKMz self perpetuates.

A
  1. Once translated, PKMz may act to remove repressors on other transcripts encoding for more PKMz.
  2. In response to chemically induced synaptic actvity, PKMz translocates from the cytosol to the nucleus to ensure that levels of PKMz are available to maintain the potentiated synapses.
92
Q

How does the drug Zip affect PKMz?

A

Zip functions as an inhibitory domain and inactivates it. Zip reverses the effect of potentiated synapses.

93
Q

What replaces the GluA1 receptors to maintain LTP?

A

The immediate induction of LTP is due to trapping GluA1 receptors in the PSD, but they are soon replaced by GluA2.

94
Q

How does PKMz regulate LTP maintenance through GluA2 receptors?

A

A pool of GluA2 receptors is trapped outside of the synapse by PICK1. Release of this pool depends on a trafficiking protein enzyme, NSF. When PKMz interacts with the NSF-PICK1 complex, the receptors are released for entry into the PSD.

95
Q

How does PKMz interfere with normal endocytotic processes to help maintain LTP?

A

The activation of Trk receptors phosphorylates GluA2 receptors to release the receptors form the PSD into the endocytotic zone where they bond with the NSF-PICK1 complex for recycling. The presense of PKMz disrupts the normal endocytic cycle- the phosphorylated receptors remain trapped in the PSD and the synapse remain potentiated.

Trk phosphorylation is like calling your mom to come pick you up. PKMz is why your mom is busy and can’t come pick you up.

96
Q

What are the 3 main roles of PKMz?

A
  1. Facilitate the release of nonsynaptic pools of GluA2 receptors to replace GluA1 receptors
  2. PKMz interferes with the endocytic cycle that normally removes GluA2s from the synapse
  3. PKMz clusters PSD-95 in the postsynaptic density to trap GluA2 receptors in the PSD
97
Q

What happens when you remove the gene for PKMz, what did this show?

A

Whe the gene for PKMz is deleted, LTP can be maintained by another kinase, PKC/L. These results indicate that PCK/L can compensate for the absense of PKMz, but it does not contribute to maintenance when PKMz is present.

98
Q

What are the contributions of actin to LTP maintenance?

A

To endure LTP, the inducing stimulus must intiate actin management processes that enlarge and stabalize the actin cytoskeleton in the dendritic spine. These structural changes allow enlarged spines to capture and replace proteins - allowing them to self-perpetuate.

99
Q

Does inhibiting polymerization prevent initial spine enlargement ?

A

No, the spine will intially enlarge but cannot be sustained.

100
Q

True or False

Dendritic protein synthesis is not sufficient to produce relatively long lasting LTP.

A

False

101
Q

What is a major feature of the genomic signaling hypothesis?

A

It assumes that transcripts (mRNA) needed to sustain LTP are produced as a direct consequence of neural activity associated with the stimulus that induces LTP.

102
Q

What two major findings illustrate the important role local protein synthesis plays in L-LTP?

A

1) Stimulation delivered to the Schaffer collateral fibers can produce a relatively long-lasting LTP in dendrites separated from the soma.
2) Emetine selectively delivered to the soma does not influence L-LTP.

103
Q

What are TOP mRNAs? Explain how they enhance translation capacity.

A

Terminal oligopyrimidine tract RNAs that encode for proteins such as ribosomal proteins and elongation factors, which are part of the translation machinery. They are needed to synthesize other proteins that have specific synaptic functions.

104
Q

What are the two main goals of the consolidation stage?

A

1) To initiate the synthesis of new proteins
2) to consolidate the net gain in AMPA receptors.

Neurobiology of Learning & Memory (5 decks)

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