Molecular Mechanisms of Long-Term Potentiation
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What is the function of the liquid-liquid phase separation of CaMKII, as mentioned in the content?

  • It is a mechanism used to trigger the expression phase of LTP.
  • It is a novel mechanism involved in Long-Term Potentiation (LTP). (correct)
  • It is involved in the induction phase of LTP.
  • It controls the maintenance phase of LTP.

    • Which of the following is a step involved in LTP as discussed in the text?

  • Maintenance (correct)
  • Inversion
  • Suppression
  • Repression

    • What does the term "induction" refer to in the context of LTP?

  • The long-term strengthening of synaptic connections.
  • The process by which a signal activates cellular signaling pathways. (correct)
  • The maintenance of the strengthened synaptic connections.
  • The immediate changes that occur at the synapse.

    • What is the primary focus of the book referenced by the author in 1949?

    <p>How learning and memory processes are stored in the brain. (C)</p> Signup and view all the answers

    What is the proposed mechanism by which Hebb's model explains learning and memory?

    <p>Repeated stimulation of a neuron increases its efficiency in transmitting signals. (B)</p> Signup and view all the answers

    What is the significance of the term "efficiency" as used in the context of Hebb's model?

    <p>The strength of a connection between two neurons. (A)</p> Signup and view all the answers

    What is the relationship between CaMKII and other effector proteins?

    <p>CaMKII and effector proteins activate each other in a reciprocal manner. (B)</p> Signup and view all the answers

    What is the role of CaMKII in maintaining the strength of synaptic connections as discussed in the text?

    <p>CaMKII is involved in processes that strengthen synaptic connections. (A)</p> Signup and view all the answers

    Which study examined the impact of reduced NMDA receptor expression on mouse behavior?

    <p>Mohn et al., 1999 (B)</p> Signup and view all the answers

    What is the primary focus of the study by N.E. et al., 2014?

    <p>Examining the balance and stability of synaptic structures during plasticity (A)</p> Signup and view all the answers

    Which study explored the role of GluR1 phosphorylation in synaptic plasticity?

    <p>Lee et al., 2003 (C)</p> Signup and view all the answers

    What technique was used to create a probe for fluorescence lifetime imaging of CaMKII activity in the study by Kwok et al., 2008?

    <p>Genetically encoded probes (B)</p> Signup and view all the answers

    In the context of synaptic plasticity, what does the study by Larkman et al., 1992, suggest about presynaptic release probability?

    <p>It influences where long-term potentiation occurs (C)</p> Signup and view all the answers

    According to the study by Miller et al., 1988, which receptors play a role in the induction and expression of long-term potentiation?

    <p>Both AMPA and NMDA receptors (D)</p> Signup and view all the answers

    The study by Miyawaki, 2005, focused on which aspect of brain function?

    <p>Imaging brain function using fluorescent proteins (C)</p> Signup and view all the answers

    Which study investigated the molecular basis of intellectual disability?

    <p>Yang et al., 2017 (A)</p> Signup and view all the answers

    Which of these is NOT a characteristic of Hebbian synaptic plasticity?

    <p>A process that is solely dependent on the diffusion and turnover of component molecules. (B)</p> Signup and view all the answers

    What is the primary role of NMDA receptors in synaptic transmission?

    <p>They are primarily involved in the induction of long-term potentiation (LTP). (C)</p> Signup and view all the answers

    Which of the following researchers conducted experiments that provided the first experimental demonstration of Hebbian plasticity in an animal?

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

    Why is in vitro hippocampal slice preparation considered advantageous for studying LTP?

    <p>It allows for easier manipulation and control of synaptic activity. (A)</p> Signup and view all the answers

    What is the specific phenomenon that Hebbian plasticity refers to?

    <p>The strengthening of synapses due to coincidental pre- and post-synaptic activity. (D)</p> Signup and view all the answers

    What is the primary role of AMPA receptors in basal synaptic transmission?

    <p>They mediate the majority of synaptic transmission signals. (B)</p> Signup and view all the answers

    Which of the following is NOT a mechanism that contributes to the maintenance of LTP?

    <p>The diffusion and turnover of synaptic molecules. (A)</p> Signup and view all the answers

    What is the core concept behind the term “expression” in the context of Hebbian synaptic plasticity?

    <p>The biochemical changes triggered by signaling that lead to enhanced synaptic transmission. (B)</p> Signup and view all the answers

    What role does calcium/calmodulin-dependent protein kinase II play in neuron function?

    <p>Facilitates synaptic Ca2+ signaling (A)</p> Signup and view all the answers

    What is the effect of repeated stress on cognitive function as suggested in the content?

    <p>Suppresses glutamate receptor expression (A)</p> Signup and view all the answers

    What is a key finding related to nitric oxide and carbon monoxide regarding synaptic enhancement?

    <p>They induce activity-dependent long-term synaptic enhancement (D)</p> Signup and view all the answers

    Which of the following techniques is used to visualize synaptic calcium signaling in neurons?

    <p>Fluorescence resonance energy transfer microscopy (B)</p> Signup and view all the answers

    What phenomenon occurs due to the alignment of trans-synaptic nanocolumns?

    <p>Enhanced receptor activation by neurotransmitters (B)</p> Signup and view all the answers

    What role does calcium/calmodulin-dependent kinase II play in synaptic plasticity?

    <p>It phosphorylates the GluR1 subunit of AMPA receptors. (D)</p> Signup and view all the answers

    Which factor is critical for AMPA receptor expression in hippocampal pyramidal neurons?

    <p>Dendritic spine geometry (B)</p> Signup and view all the answers

    What hypothesis suggests that specific synaptic events can 'tag' synapses for later potentiation?

    <p>The capture hypothesis (B)</p> Signup and view all the answers

    What is the function of the Ras-like GTPase Rem2 in relation to calcium/calmodulin-dependent kinase II?

    <p>It inhibits the kinase's activity. (B)</p> Signup and view all the answers

    Which process is directly revealed by analyzing miniature synaptic currents?

    <p>Post-synaptic contributions to long-term potentiation (B)</p> Signup and view all the answers

    What does the phosphorylation and regulation of glutamate receptors depend on?

    <p>Calcium/calmodulin-dependent protein kinase II (B)</p> Signup and view all the answers

    Which of the following studies focused on the structural basis of long-term potentiation?

    <p>Matsuzaki, M., et al., 2004 (C)</p> Signup and view all the answers

    What is one of the key findings from the study on postsynaptic contributions to long-term potentiation?

    <p>Long-term potentiation involves changes in postsynaptic current dynamics. (C)</p> Signup and view all the answers

    What is one role of Ca2+/calmodulin-dependent protein kinase II in relation to synaptic activity?

    <p>Facilitates structural long-term potentiation (A)</p> Signup and view all the answers

    What mechanism is suggested to underlie post-tetanic potentiation?

    <p>Swelling of dendritic spines (B)</p> Signup and view all the answers

    Which process is examined in the context of cGMP's role in long-term potentiation?

    <p>Its modulation of ion channel activity (A)</p> Signup and view all the answers

    What was identified adjacent to the inhibitory and calmodulin-binding domains of CaMKII?

    <p>A phosphorylation site (D)</p> Signup and view all the answers

    Which neurotransmitter's transporter is affected by the blockade that potentiates postsynaptic excitation?

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

    What is the primary focus of the study by Shen et al. regarding CaMKII?

    <p>Dynamic control of translocation and localization (C)</p> Signup and view all the answers

    What type of dependency does CaMKII exhibit in its functionality?

    <p>Calcium-dependent (B)</p> Signup and view all the answers

    What role does the study suggest for NMDA receptor stimulation in neurons?

    <p>Regulating CaMKII activity (D)</p> Signup and view all the answers

    Study Notes

    Molecular Mechanism of Hippocampal Long-Term Potentiation

    • Long-term potentiation (LTP) is a cellular process thought to underlie learning and memory
    • Postsynaptic NMDA receptor activation triggers AMPA receptor and protein trafficking to synapses
    • Spine enlargement occurs alongside actin modulation (structural LTP or sLTP) during LTP
    • Maintaining LTP despite protein turnover is a key research focus
    • Ca²⁺ influx through NMDA receptors activates kinases like Ca²⁺/calmodulin-dependent protein kinase II (CaMKII)
    • CaMKII can sustain long-term signaling via a reciprocally-activating complex with its substrate proteins, including Tiam1
    • This regulation helps maintain downstream signalling
    • CaMKII can condense at the synapse through liquid-liquid phase separation (LLPS)
    • LLPS increases binding capacity at the synapse, supporting expanded protein complexes
    • LLPS may function as a synapse tag to capture newly synthesized proteins

    First Step of LTP: Induction

    • LTP occurs in three phases: induction, expression, and maintenance
    • Induction is triggered by tetanic stimulation, altering synapse function
    • This leads to increased synaptic transmission (expression)
    • Maintenance mechanisms sustain this enhanced transmission despite component turnover and reverse reactions

    Debate on Pre- or Postsynaptic Expression and Maintenance of LTP

    • Whether LTP is presynaptic (increased transmitter release) or postsynaptic (increased sensitivity to glutamate) was debated early
    • Studies used radiolabeled glutamate, which suggested presynaptic enhancement
    • Quantal analysis also supported presynaptic involvement
    • Independent measures now show postsynaptic LTP expression, notably AMPA receptor changes
    • Postsynaptic changes necessitate retrograde communication, possibly involving diffusible messengers (e.g., NO, CO, arachidonic acid)

    AMPA Receptor Trafficking

    • Advancements in technologies like neural gene introduction and fluorescence microscopy have aided LTP studies
    • AMPA receptor translocation to the synapse is key to LTP expression and maintenance
    • Lateral diffusion and exocytosis of AMPA receptors play roles in this translocation

    Structural LTP

    • LTP is linked to changes in dendritic spine structure (structural LTP, or sLTP)
    • Tetanic stimulation triggers early spine enlargement, a process that can last several hours
    • sLTP is linked to NMDA receptor activation
    • Observations from in vivo studies, in addition to electrical recordings, demonstrated that spines undergo morphological changes

    Trafficking of Various Proteins

    • Many molecules, including receptors and signaling proteins, experience regulated trafficking during LTP
    • This trafficking is crucial for maintaining synaptic function

    Cellular Signaling Leading to LTP

    • CaMKII is a key signaling molecule in LTP induction and maintenance
    • Postsynaptic Ca²⁺ influx activates CaMKII
    • Genetic ablation or inhibition of CaMKII impairs LTP and memory
    • CaMKII can phosphorylate other proteins like AMPA receptors, enhancing synapse function
    • The constitutive activity of CaMKII, even under basal conditions, is important for maintenance of LTP

    Possible Substrates of CaMKII

    • AMPA receptors, NMDA receptor subunits, Neuroligin, Shank, and other proteins are possible targets of CaMKII
    • Phosphorylation of specific sites on certain proteins (e.g., AMPA receptor S831) may be vital for LTP expression

    Liquid-Liquid Phase Separation of CaMKII

    • CaMKII aggregation through liquid-liquid phase separation (LLPS) occurs within a synapse
    • This LLPS process can result in the formation of synaptic nanodomains
    • The temporary Ca²⁺ signal can be persistently remembered through LLPS condensates
    • The formation of different protein phases within a synapse is important for LTP maintenance

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    Related Documents

    Molecular Mechanism of Hippocampal LTP: Learning and Memory (PDF)

    Description

    This quiz explores the molecular mechanisms behind long-term potentiation (LTP) in the hippocampus, a process crucial for learning and memory. Key concepts include NMDA receptor activation, CaMKII signaling, and structural changes in synapses. Test your understanding of the intricate cellular processes that enable memory consolidation.

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