CaMKII and Synaptic Plasticity
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Questions and Answers

What role does CaMKII play in the interaction with F-actin structures?

  • It stabilizes F-actin structures. (correct)
  • It inhibits F-actin polymerization.
  • It has no impact on F-actin structures.
  • It destabilizes F-actin structures.

How does CaMKII activity specifically impact synapse volumes after stimulation?

  • It leads to persistent increases in spine volume. (correct)
  • It decreases spine volume immediately.
  • It causes a transient increase in spine volume.
  • It has no effect on spine volume at all.

What characterizes the state of retinotectal synapses during early development?

  • They exhibit high levels of CaMKII activity.
  • They are rich in AMPA receptors.
  • They are primarily silent and lack AMPA receptors. (correct)
  • They show persistent activation of CaMKII.

What consequence arises from the activity-dependent binding of CaMKII to NR2B?

<p>It triggers F-actin re-structuring and affects spine size. (B)</p> Signup and view all the answers

What is indicated by the transient activation of CaMKII observed after local glutamate uncaging?

<p>It indicates specific increases in CaMKII activity at stimulated spines. (C)</p> Signup and view all the answers

What is the primary role of CaMKII in the context of learning and memory?

<p>Modulating the structure and strength of synaptic connections (D)</p> Signup and view all the answers

Which of the following accurately describes the function of CREB?

<p>It is involved in long-term potentiation and excitability modulation (A)</p> Signup and view all the answers

What distinguishes IEGs from other gene types in the context of synaptic activity?

<p>They encode proteins that are immediate responses to neuronal activity (C)</p> Signup and view all the answers

Which statement about BDNF (Brain-Derived Neurotrophic Factor) is true?

<p>It supports the survival and differentiation of neurons (A)</p> Signup and view all the answers

Regarding the postsynaptic density, which statement about CaMKII's presence is accurate?

<p>CaMKII represents a small percentage (1-2%) of the brain's total protein content (A)</p> Signup and view all the answers

In the context of synaptic plasticity, what does 'engrams' refer to?

<p>The physical manifestation of memory in neuron structures (B)</p> Signup and view all the answers

What is the primary mechanism through which CaMKII contributes to the late phase of long-term potentiation?

<p>Through the phosphorylation of specific substrates leading to increased synaptic strength (C)</p> Signup and view all the answers

What is the primary function of CaMKII in the postsynaptic density?

<p>It is involved in synaptic signaling and modulation. (C)</p> Signup and view all the answers

How many isoforms comprise the CaMKII family derived from the four genes?

<p>28 (C)</p> Signup and view all the answers

What role do the α- and β-subunits of CaMKII primarily play in the brain?

<p>They are the predominant isoforms. (B)</p> Signup and view all the answers

What type of structure does CaMKII exhibit with its 12 subunits?

<p>Two hexameric rings (D)</p> Signup and view all the answers

What is the key mechanism by which CaMKII maintains its activity?

<p>It associates with calmodulin and calcium ions. (C)</p> Signup and view all the answers

Which of the following is NOT a role of CaMKII?

<p>Generating new neuronal structures. (A)</p> Signup and view all the answers

What aspect of CaMKII allows it to bind anchoring proteins?

<p>Association domain (D)</p> Signup and view all the answers

What modification does CaMKII carry out regarding Ca2+/calmodulin sensitivity?

<p>Enhanced sensitivity (B)</p> Signup and view all the answers

Which of the following correctly describes the 'gate' function of CaMKII?

<p>It regulates the association with the catalytic domain. (A)</p> Signup and view all the answers

What occurs within less than 1 second after a decrease in Ca2+ levels?

<p>Calmodulin dissociates (B)</p> Signup and view all the answers

What mechanism allows for short-term persistent activation of CamKII?

<p>Autophosphorylation of Thr286 (C)</p> Signup and view all the answers

Under what condition does long-term persistent activation occur in the context of LTP?

<p>Threshold number of kinase sites are phosphorylated (B)</p> Signup and view all the answers

What role does CamKII play in the context of LTP and synaptic transmission?

<p>It enhances synaptic transmission (B)</p> Signup and view all the answers

What condition must be met for a CamKII persistent activity to decline?

<p>Dephosphorylation of Thr286 (B)</p> Signup and view all the answers

What happens during the perfusion of active CaMKII on CA1 pyramidal cells?

<p>Increase in amplitude of spontaneous synaptic potentials (A)</p> Signup and view all the answers

What occurs when the rate of autophosphorylation exceeds dephosphorylation?

<p>A long-lasting 'on' state of the switch is achieved (D)</p> Signup and view all the answers

What is suggested by increased transmission in the non-LTP group after perfusion of active CaMKII?

<p>Occlusion between CaMKII-induced potentiation and LTP induction (D)</p> Signup and view all the answers

What is the predominant function of IEGs in the context of memory and learning?

<p>They establish engrams related to LTP (A)</p> Signup and view all the answers

What is the primary subtype of NMDAR with which CaMKII associates?

<p>NR2B (A)</p> Signup and view all the answers

What effect does calcium elevation have on CaMKII's association with F-actin?

<p>It causes CaMKII to dissociate from F-actin. (B)</p> Signup and view all the answers

After CaMKII binds to NR2B, which of the following is true about its activity?

<p>It remains active even after dissociation of Ca2+/calmodulin. (B)</p> Signup and view all the answers

What is one consequence of NR2B acting as a wedge in the autoinhibitory gate?

<p>Prevention of secondary autophosphorylation at Thr305. (A)</p> Signup and view all the answers

Which site on GluR1 is specifically phosphorylated by CaMKII to enhance AMPA receptor conductance?

<p>Ser831 (C)</p> Signup and view all the answers

What role does the T site play in CaMKII activation after binding to NR2B?

<p>It keeps the autoinhibitory gate open. (B)</p> Signup and view all the answers

What happens to CaMKII's activity after it phosphorylates AMPA receptors?

<p>It enhances conductance at the synapse. (A)</p> Signup and view all the answers

Under resting conditions, what effect does F-actin have on CaMKII?

<p>It sequesters CaMKII away from synapses. (D)</p> Signup and view all the answers

What is a significant function of CaMKII in synaptic mechanisms?

<p>Enhancing channel conductance of AMPA receptors. (A)</p> Signup and view all the answers

Which of the following statements regarding CaMKII's activation is incorrect?

<p>It is sensitive to phosphatase activity. (A)</p> Signup and view all the answers

Flashcards

CaMKII

A protein kinase involved in the regulation of synaptic plasticity and learning processes.

CaMKII location

CaMKII is found in high concentrations in the postsynaptic density, the specialized region of the synapse where neurotransmitter receptors are located.

Late-phase LTP

A long-lasting form of synaptic strengthening that plays a crucial role in memory formation.

CREB

A transcription factor that regulates the expression of genes involved in synaptic plasticity.

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Immediate early genes (IEGs)

Genes that are rapidly induced in response to neuronal activity, playing a critical role in synaptic plasticity and memory formation.

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Arc

A specific IEG that is involved in the consolidation of memories.

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BDNF

A protein that plays a role in neuronal growth, survival, and synaptic plasticity.

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What are CaMKII isoforms?

A family of protein kinases that are important for synaptic plasticity and learning, with 28 similar isoforms derived from four genes (α, β, γ and δ).

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Which CaMKII subunits are most prevalent in the brain?

The α- and β-subunits are the most common types of CaMKII found in the brain, playing a key role in synaptic function.

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What is the function of the association domain in CaMKII?

A specific region within the CaMKII molecule that binds to anchoring proteins, guiding it to specific locations within the cell.

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What is the role of the gate in CaMKII activity?

A region of the CaMKII molecule that acts like a gate, controlling the enzyme's activity and sensitivity to Calcium and calmodulin.

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Describe the structure of the CaMKII holoenzyme.

A structure formed by 12 CaMKII subunits, where the catalytic and regulatory domains create two hexameric rings linked by a stalk.

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What are the ATP and substrate binding sites in CaMKII?

Regions within the CaMKII molecule responsible for binding ATP and target substrates, enabling the phosphorylation process.

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What is CREB and what is its role in memory formation?

A key transcription factor involved in long-term potentiation (LTP) and regulating neuronal excitability. It plays a crucial role in memory formation.

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What are immediate early genes (IEGs)?

Genes that are rapidly activated in response to neuronal activity, playing a crucial role in synaptic plasticity and memory formation.

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What is Arc and what is its role in memory formation?

A specific IEG that is involved in the consolidation of memories and may act as a novel signaling molecule.

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What is CaMKII?

A type of protein kinase that plays a crucial role in long-term potentiation (LTP) and learning processes.

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How does CaMKII respond to decreasing calcium levels?

CaMKII dissociates rapidly from the complex when calcium levels drop.

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What is causing long-term CaMKII activation?

This long-term activation occurs when the rate of autophosphorylation surpasses the rate of dephosphorylation.

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How does CaMKII affect synaptic transmission?

CaMKII has the ability to enhance synaptic transmission by increasing the amplitude of spontaneous synaptic potentials.

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What is the relationship between CaMKII and LTP?

LTP is a type of synaptic strengthening, and CaMKII is essential for its development.

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What do experiments involving CaMKII perfusion and LTP indicate?

This suggests that LTP relies on CaMKII for its induction, as they share a similar mechanism.

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What does CaMKII-induced potentiation suggest about LTP induction?

This effect is seen in both the absence and presence of LTP, indicating common pathways.

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What is the impact of autophosphorylation on CaMKII activity?

CaMKII's ability to autophosphorylate Thr286 allows it to maintain activity even after calcium levels drop, but this effect is transient and can be reversed by dephosphorylation.

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How does the interplay of phosphorylation and dephosphorylation impact CaMKII activity?

This switch-like behavior happens when phosphorylation exceeds the rate of dephosphorylation, enabling sustained CaMKII activity for long periods.

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Why is CaMKII persistent activity crucial for long-term memory formation?

CaMKII's persistent activity, which involves autophosphorylation and the balance between phosphorylation and dephosphorylation, is crucial for long-term memory formation.

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How does CaMKII regulate spine size?

CamKII can regulate the size of a synapse by interacting with F-actin, a protein that forms the cytoskeleton of the spine. This interaction allows CamKII to affect the shape and size of the spine, influencing the strength and efficiency of synaptic transmission.

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CaMKII-NR2B interaction

CaMKII interacts with the NR2B subunit of NMDA receptors, contributing to its own persistent activation. This interaction is crucial for maintaining CaMKII activity even after the initial calcium influx subsides, ensuring prolonged synaptic strengthening.

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CaMKII - F-actin binding

Under normal conditions, the beta-subunit of CaMKII is held away from synapses by F-actin. But a rise in calcium causes CaMKII to detach from F-actin and move towards the synapse.

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CaMKII activation and NR2B binding

CaMKII activation, even without autophosphorylation, increases its binding to the cytoplasmic C-terminal of the NR2B subunit.

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NR2B - autoinhibitory mimic

A region on the NR2B subunit resembles the autoinhibitory domain and binds to the T site of CaMKII. This binding blocks the autoinhibitory gate, maintaining CaMKII activation even after calcium levels decline.

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CaMKII - sustained effects

CaMKII's sustained activation due to its interaction with NR2B has several consequences: it resists deactivation by phosphatases, blocks further autophosphorylation at Thr305, and promotes further autophosphorylation within the CaMKII ring.

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CaMKII - AMPA receptor phosphorylation

CaMKII directly enhances the conductance of AMPA receptors present at the synapse. This strengthens synaptic transmission, promoting long-lasting changes in synaptic strength.

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CaMKII - GluR1 phosphorylation

CaMKII phosphorylates the GluR1 subunit of AMPA receptors at Ser831, a specific site that increases the channel's conductance.

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CaMKII - LTP consolidation

CaMKII, through its ability to phosphorylate AMPA receptors and maintain its own activity, plays a critical role in the consolidation and maintenance of long-term potentiation (LTP).

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CaMKII, NR2B, and LTP

The persistent activation of CaMKII, facilitated by its interaction with NR2B, contributes to the long-lasting nature of LTP, essential for memory formation.

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CaMKII - CREB activation

CaMKII's ability to activate the transcription factor CREB, through its interaction with other signaling pathways, influences gene expression involved in synaptic plasticity, ultimately contributing to LTP and memory formation.

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How does CaMKII interact with NMDA receptors?

CaMKII can bind to the NR2B subunit of NMDA receptors, which helps to maintain its activity even after calcium levels decline.

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What happens to CaMKII when it's activated?

When CaMKII is activated, it can detach from F-actin and move towards the synapse. This is important for strengthening the synapse.

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What keeps CaMKII away from synapses?

The beta-subunit of CaMKII is normally held away from synapses by F-actin, a protein that helps to maintain the structure of the synapse.

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What can CaMKII affect?

CaMKII can regulate the size of a synapse by interacting with F-actin, a protein that forms the backbone of the synapse.

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How does CaMKII affect AMPA receptors?

CaMKII can directly enhance the conductance of AMPA receptors present at the synapse, which strengthens synaptic transmission and promotes long-lasting changes in synaptic strength.

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Study Notes

Molecular Basis of Synaptic Plasticity II

  • CamKII: Has a crucial role in learning and memory, contributing to synaptic plasticity
  • Structure and Function: Plays a key role in synaptic signaling and modulation.
  • Mechanisms: Mediates various processes contributing to synaptic function and plasticity.
  • Contribution to Learning and Memory: Central to the biological mechanisms underlying memory formation.

CREB

  • Definition: Crucial in regulating gene expression in response to various signals, including those involved in learning and memory.
  • LTP and Synaptic Capture: Critical to understanding long-term synaptic plasticity, a key element in learning.
  • Excitability: Aids in regulating neuron excitability and synaptic strength.

IEGs

  • Definition: A category of genes with rapid and transient expression in response to external stimuli.
  • Engrams and LTP: IEGs are critical to long-term memory formation, a significant aspect of synaptic plasticity.
  • Excitability: Affects the excitatory properties of neurons.
  • Arc and a novel mode of transmission: Arc facilitates the establishment of long-term memory, using a unique pathway for information transfer.

BDNF

  • Definition: Regulates various aspects of neuronal function and plasticity.
  • BDNF can Induce LTP: A key regulator of LTP induction, it contributes to memory formation.
  • Necessary for Spatial Learning: Essential for spatial learning, showing its crucial role in memory processes.

CamKII Activation States

  • Brief Activation: No autophosphorylation, short-lived effect.
  • Short-term Persistent Activation: Autophosphorylation, lasting activation even after calcium levels decrease.
  • Long-term Persistent Activation: Very prolonged activation, achieved by a rate of autophosphorylation dominating the dephosphorylation process. This is important for long-term memory.

From LTP to CaMKII

  • Pathways in the Schaffer collateral pathway: Illustrates the complex interactions between CREB, MAPK, PKA, protein phosphatase 1, and other signaling molecules during synaptic plasticity.
  • Role of Modulatory Inputs (e.g., dopamine): External influences on these complex pathways, influencing synaptic activity and plasticity.

CAMKII Structure

  • Structure and Classification: The details of multiple protein isoforms derived from four genes (alpha, beta, gamma and delta) are elaborated. Importance of each subunit to overall function.
  • Catalytic and Regulatory Domains: Essential structural details, catalytic/regulatory domains forming hexameric rings and the gear-shaped association domain, which influence catalytic function.

Mechanisms to Impact Transmission

  • Association with NMDARs: Interactions with NMDA receptors, particularly NR2B, are primary mechanisms.
  • Phosphorylation of AMPARs: The phosphorylation of AMPA receptors (especially at Ser831 on GluR1) is extensively described.
  • Regulation of AMPAR Trafficking: The process of regulating AMPA receptor movement to and from synapses is elaborated, using proteins like SAP97 and Myosin VI
  • Regulation of Function and Trafficking of AMPARs: The roles of SAP97/Myosin VI and Stargazer proteins in regulating AMPA receptors are outlined.
  • Regulation of spine size: Specific pathways influence spine size via interaction of CaMKII with F-actin.

CamKII in vivo: Synaptic Maturation

  • Early Development and Synaptic Function: Details how synapses operate during early development in vivo.
  • Activity-dependent Changes: The effects of activity on synapse function.

CREB Inhibition Leads to Long-term Deficits

  • Long-Term vs. Short-Term Memory Involvement: Illustrates differing effects on long-term and short-term memory.
  • CREB Mutations and Memory: Details the consequences of disrupting CREB activity on memory consolidation or reconsolidation via genetic manipulation.
  • CREB Activation Mechanisms: Describe mechanisms by which CREB is often activated in response to incoming signals.

Immediate Early Genes (IEGs)

  • Quick Expression and Turnover: Highlight IEGs as rapidly expressed genes which have short half-lives.
  • Pattern of Activity Leading to IEG Expression: The relationship between synaptic activity and the expression of specific IEGs is detailed.

Engrams and the Locus of Memory

  • Historical Perspectives: Provides historical context and background on concepts of memory representations.
  • Mechanisms of Memory Consolidation Evidence: Evidence relating to the physical location of long term memory.
  • Key Figures in Memory Research: Highlights important figures in memory research.

BDNF

  • Neurotrophic Factor Properties: The details of a particular neurotrophin, its effects on various processes (proliferation, survival, repair, and plasticity) during neuronal development, and its implications for plasticity during development.
  • BDNF and LTP: Show how BDNF contributes to long-term potentiation by inducing relevant proteins.
  • BDNF and Spatial Learning: Details the specific role of BDNF as a key factor for spatial learning.

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Description

This quiz explores the multifunctional role of CaMKII in synaptic plasticity, with a focus on its interactions with F-actin structures and implications for learning and memory. Questions delve into various mechanisms, including the activity-dependent binding to NR2B, the role of CREB, and the significance of IEGs. Test your understanding of these critical neurobiological processes.

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