Molecular Basis of Synaptic Plasticity I
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What does LTP primarily achieve in neuronal communication?

  • Obliterating synaptic pathways
  • Weakening of synaptic transmission
  • Normalizing neurotransmitter levels
  • Strengthening of synaptic transmission (correct)

    • Which role do second-messenger signaling pathways play in LTP?

  • They have no significant impact on synaptic processes
  • They only affect postsynaptic cell sensitivity
  • They prevent receptor activation altogether
  • They alter neurotransmitter release in the presynaptic cell (correct)

    • Which factor is NOT essential in distinguishing different types of LTP?

  • Type of receptors involved
  • Type of ion channels involved
  • Mechanism of neurotransmitter synthesis (correct)
  • Second-messenger signaling pathways

    • What is the effect of NMDA receptor antagonists like APV on LTP?

    <p>They completely block LTP</p> Signup and view all the answers

    What cellular alteration does presynaptic LTP involve?

    <p>Increased calcium influx through L-type Ca2+ channels</p> Signup and view all the answers

    Which of the following is associated with the concept of experience-dependent plasticity within LTP?

    <p>The structural alterations of synapses due to learning</p> Signup and view all the answers

    Which type of AMPARs is directly linked to the mechanisms of LTP?

    <p>Calcium permeable AMPARs</p> Signup and view all the answers

    What is one of the initial triggers in the process of inducing presynaptic LTP?

    <p>Tetanus stimulation</p> Signup and view all the answers

    What is the initial step that leads to increased glutamate release in the process of LTP in the Mossy Fiber?

    <p>Large Ca2+ influx into the presynaptic terminal</p> Signup and view all the answers

    In classical conditioning, what role does the calcium/calmodulin-dependent adenylyl cyclase play?

    <p>It serves as a coincidence detector</p> Signup and view all the answers

    Which factor is responsible for further potentiation of cAMP production following a tail shock in classical conditioning?

    <p>Release of 5-HT onto the sensory neuron</p> Signup and view all the answers

    What is the consequence of RIM1α knockout in relation to Mossy Fiber LTP?

    <p>Abrogation of LTP in Mossy Fibers</p> Signup and view all the answers

    What is the role of PKA in the process of LTP following the large Ca2+ influx?

    <p>It stimulates the production of cAMP</p> Signup and view all the answers

    Which step is NOT involved in the mechanism of LTP triggered by calcium influx?

    <p>Inhibition of presynaptic vesicle release</p> Signup and view all the answers

    What effect does increased cAMP production have on the synapse during presynaptic facilitation?

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

    What triggers the action potential (AP) in the sensory neuron during the classical conditioning process?

    <p>Siphon touch</p> Signup and view all the answers

    What is one of the key features of long-term potentiation (LTP) related to memory?

    <p>It can last for days or even weeks.</p> Signup and view all the answers

    Which of the following correctly describes the relationship between conditioned and unconditioned stimuli in the context of LTP?

    <p>Conditioned stimuli can be strengthened through LTP when paired with unconditioned stimuli.</p> Signup and view all the answers

    What role do calcium permeable AMPARs play in synaptic plasticity?

    <p>They facilitate postsynaptic strengthening during synaptic activity.</p> Signup and view all the answers

    How do LTD protocols differ from LTP protocols in behavioral responses?

    <p>LTD protocols reverse prior conditioning effects.</p> Signup and view all the answers

    In the context of LTP's role in memory, which of the following statements is true?

    <p>The mechanism of LTP suggests a causal link to memory storage.</p> Signup and view all the answers

    What type of stimuli can optical conditioning involve in the context of LTP?

    <p>Both auditory and visual stimuli.</p> Signup and view all the answers

    Which of the following best defines the purpose of optical CS pairing in the context of LTP?

    <p>To strengthen synaptic connections in specified pathways.</p> Signup and view all the answers

    What is the significance of the medial geniculate nucleus in optical CS pairing?

    <p>It is involved in auditory processing linked to conditioned stimuli.</p> Signup and view all the answers

    What role does PKMζ play in the maintenance of long-term potentiation (LTP)?

    <p>It enhances the actions of NSF to prevent removal of GluA2.</p> Signup and view all the answers

    Which process is crucial for the late phase of LTP in the Schaffer collateral pathway?

    <p>PKA-mediated activation of CREB for structural changes.</p> Signup and view all the answers

    What is the significance of PKMζ lacking a regulatory domain?

    <p>It ensures PKMζ is constitutively active without external signals.</p> Signup and view all the answers

    What triggers the increase in translation of PKMζ mRNA in CA1 neurons during LTP?

    <p>Tetanic stimulation.</p> Signup and view all the answers

    Which of the following occurs during early long-term potentiation (LTP)?

    <p>Activation of NMDA receptors and subsequent Ca2+ influx.</p> Signup and view all the answers

    How does the influx of Ca2+ contribute to structural changes in the late phase of LTP?

    <p>By activating local translation of mRNA.</p> Signup and view all the answers

    What is the effect of tetanic stimulation on PKMζ levels?

    <p>It increases the local translation of PKMζ mRNA.</p> Signup and view all the answers

    What is primarily responsible for the formation of new presynaptic release sites in LTP?

    <p>The clustering of new AMPA receptors on postsynaptic membranes.</p> Signup and view all the answers

    What is the characteristic of GluA2-lacking AMPARs in terms of conductance?

    <p>Decreased conductance at positive potentials</p> Signup and view all the answers

    What subunit composition is indicated for AMPARs related to experience-dependent plasticity?

    <p>GluA1, GluA3, and GluA4</p> Signup and view all the answers

    In the context of fear conditioning, what accumulates in the lateral amygdala (LA)?

    <p>GluA2-lacking AMPARs</p> Signup and view all the answers

    What effect does reconsolidation update have on fear memories?

    <p>Erases fear memories in various species</p> Signup and view all the answers

    What is the role of cp-AMPARs in synaptic plasticity?

    <p>Promotion of the synaptic response through increased calcium permeability</p> Signup and view all the answers

    Which study investigated the effectiveness of reconsolidation update in various species?

    <p>Schiller et al., Nature 2010</p> Signup and view all the answers

    What is the role of PICK1 in the context of cp-AMPAR trafficking during long-term potentiation (LTP)?

    <p>Promotes the switch to synaptic cp-AMPARs</p> Signup and view all the answers

    How is the Rectification Index defined?

    <p>By the ratio of positive to negative slope conductance</p> Signup and view all the answers

    What effect does the S845A mutation have on GluA1 functionality?

    <p>Prevents GluA1 from being phosphorylated</p> Signup and view all the answers

    What feature distinguishes calcium permeable AMPARs from other AMPARs?

    <p>Absence of GluA2 subunit</p> Signup and view all the answers

    Which of the following is associated with the dephosphorylation of GluA1 at S845?

    <p>NMDAR-dependent long-term depression (LTD)</p> Signup and view all the answers

    What is the proposed effect of activation of protein kinase A (PKA) during LTP on GluA1?

    <p>Promotes phosphorylation at S845</p> Signup and view all the answers

    What role does the subunit composition of AMPARs play in their function?

    <p>Influences their permeability to calcium ions</p> Signup and view all the answers

    What is the implication of the accumulation of cp-AMPARs in fear conditioning?

    <p>It contributes to the consolidation of fear memories</p> Signup and view all the answers

    What key concept is associated with cp-AMPARs and synaptic plasticity?

    <p>They are involved in the bidirectional regulation of synaptic strength.</p> Signup and view all the answers

    Which type of AMPAR is suggested to promote synaptic activity during reconsolidation?

    <p>cp-AMPARs lacking GluA2</p> Signup and view all the answers

    How does the removal of cp-AMPARs contribute to synaptic dynamics?

    <p>It plays a role in long-term depression processes.</p> Signup and view all the answers

    What interaction occurs between GluA2 and PICK1 during LTP?

    <p>Limits AMPAR recycling to GluA2-containing AMPARs</p> Signup and view all the answers

    Which phosphorylation site on GluA1 is critical for its role in synaptic plasticity?

    <p>S845</p> Signup and view all the answers

    Study Notes

    Molecular Basis of Synaptic Plasticity I

    • Synaptic plasticity is a biological process where specific patterns of synaptic activity cause changes in synaptic strength.
    • This is thought to contribute to learning and memory.
    • Both pre-synaptic and post-synaptic mechanisms contribute.
    • LTP (long-term potentiation) is a family of processes strengthening synaptic transmission.
    • These mechanisms differ based on receptor, ion channel, and second-messenger signaling pathway importance.
    • Mechanisms are found both in pre-synaptic (altering release) and post-synaptic (sensitivity to the neurotransmitter) cells.

    Lecture Outline

    • Synaptic Plasticity
    • LTP (Long-Term Potentiation)
      • Types of LTP
      • AMPAR Trafficking
      • Stages of LTP
        • Early LTP
        • Late LTP
      • Molecular Basis of LTD (Long-term Depression)
    • LTP/LTD and Memory?
    • Experience-Dependent Plasticity
      • Calcium Permeable AMPARS

    What is Synaptic Plasticity?

    • Synaptic plasticity is the biological process by which specific patterns of synaptic activity change synaptic strength. It's thought to be a key process in learning and memory.

    Long-Term Potentiation (LTP)

    • LTP can last for days to weeks.
    • A graph shows the amplitude of population EPSPs (excitatory postsynaptic potentials) changes over time.
    • Different pathways show varying magnitudes of the response.

    LTP

    • LTP is a family of processes that strengthen synaptic transmission.
    • These processes differ based on the relative importance of various receptors, channels, and signaling pathways, either in the pre-synaptic cell (altering release) or the post-synaptic (sensitivity to the neurotransmitter) cell.

    Presynaptic LTP: Mossy Fiber

    • Large Ca2+ influx into the presynaptic terminal.
    • Activation of a calcium/calmodulin-dependent adenyl cyclase complex.
    • Activation of PKA (protein kinase A).
    • Increase in glutamate release.

    LTP in the Mossy Fiber: Non-associative

    • Large Ca2+ influx into the presynaptic terminal.
    • Activation of a calcium/calmodulin-dependent adenyl cyclase complex.
    • Activation of PKA.
    • Increase in glutamate release.

    Classical Conditioning

    • Siphon touch triggers action potentials in sensory neurons, causing Ca2+ influx in the pre-synaptic terminal.
    • Activation of Ca2+-sensitive adenyl cyclase (AC), which generates cAMP, leading to increased cAMP production.
    • Tail shock triggers further potentiation through 5-HT release.

    Vesicle Life Cycle: Docking

    • RIM binds to Munc13, and Rab3/27 to dock the vesicle, along with N, P, and Q-type Ca2+ channels.

    Postsynaptic LTP: Schaeffer Collateral

    • Normal synaptic transmission involves glutamate release from the presynaptic terminal, binding to NMDA and AMPA receptors, and subsequent membrane depolarization.
    • The induction of LTP involves increased glutamate release and postsynaptic membrane depolarization, and this process involves NMDA receptor activation and Ca2+ influx.
    • Retrograde messengers such as NO help enhance glutamate release.

    AMPAR Insertion and Silent Synapses

    • Alteration in AMPAR number is a crucial mechanism for LTP (Long-Term Potentiation) and LTD (Long-Term Depression).
    • Silent synapses are synapses where AMPA receptors are not located on the post-synaptic membrane.
    • Pairing stimuli initiates AMPA receptor insertion into post-synaptic membranes.

    AMPAR Trafficking

    • AMPARs (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) are mobile in the plasma membrane and in spines.
    • Local rises in intracellular calcium decrease GluA2 mobility and accumulate GluA2 in synapses.
    • LTD (Long-term depression) involves internalization of AMPARs.

    AMPAR trafficking: Lateralization

    • AMPARs are mobile in the plasma membrane.
    • Local rises in intracellular calcium decrease GluA2 mobility and accumulate GluA2 in synapses.
    • LTD (long-term depression) involves internalization.

    AMPAR Trafficking: Mechanisms

    • Key protein mechanisms regulating AMPAR trafficking include PSD95 and TARPS, NSF and AP2, PICK1 and ABP/GRIP, and SAP97 and Myosin VI.

    LTP vs AP2

    • The AP2 adapter complex binds to an overlapping region of GluA2.
    • NSF probably occupies this area to stabilize the receptors at synapses.

    PICK1 vs ABP/GRIP

    • PICK1 is involved in recycling AMPARs back to the plasma membrane.
    • ABP/GRIP also plays a role in the lateral movement of AMPARs within synapses.

    SAP97 and Myosin VI

    • Synapse-associated protein 97 (SAP97) binds the GluA1 PDZ domain.
    • Myosin VI is a motor protein, and the phosphorylation of SAP97 by CaMKII prompts the movement of GluA1 to synapses.

    Early vs Late LTP

    • Early-phase LTP (1-3 hours) does not need protein synthesis, while Late-phase LTP (24 hours) does require protein synthesis (including cAMP and PKA activation).

    LTP Maintenance: PKMζ

    • PKMζ (an isoform of protein kinase C) is constitutively active, maintaining LTP.
    • PKMζ enhances the actions of NSF, preventing postsynaptic removal of GluA2.

    Molecular basis of LTD

    • NMDA-LTD and mGluR5-LTD mechanisms describe different pathways leading to LTD (long-term depression).
    • There are protein phosphatase cascades and intracellular calcium changes involved in LTD (long-term depression).

    Experience-Dependent Plasticity: Fear

    • Pavlovian classical conditioning modifies synaptic transmission.
    • Fear conditioning influences thalamic afferent potentiation.

    Reconsolidation Update Successfully Erases Fear Memories in Mice, Rats, and Humans

    • Extinction-reconsolidation boundaries are key to persistent attenuation of fear memories.
    • Preventing fear return through reconsolidation update mechanisms is possible.
    • A protocol for updating involves procedures to decrease CR (conditioned response).

    Experience-Dependent Plasticity

    • Structural and functional changes in neuronal circuits based on experience (response to experience) is the topic.
    • A diagram shows the potential differences of neural response in response to environmental stimuli - suggesting modification.
    • Some animals demonstrate changes in ocular dominance based on experience.

    (cp-AMPARs and Plasticity)

    • Increased cp-AMPARs in the lateral amygdala (LA) after fear conditioning.
    • Removal of cp-AMPARs contributes to reconsolidation and memory extinction.
    • Regulation of cp-AMPAR trafficking, including mechanisms like phosphorylation, recycling and movement.

    AMPAR Subunit Composition

    • AMPAR subunit composition (GluA1-lacking and AMPAR subunits) matters in postsynaptic plasticity. -Rectification in relation to AMPAR subunit composition.

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    Molecular Basis of Synaptic Plasticity I Lecture Outline PDF

    Description

    Explore the essential concepts of synaptic plasticity, focusing on mechanisms such as long-term potentiation (LTP) and long-term depression (LTD). This quiz delves into pre-synaptic and post-synaptic processes and their roles in learning and memory. Test your understanding of the molecular basis underlying these crucial neurological processes.

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