Long-Term Potentiation (LTP)
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Questions and Answers

What is the primary role of NMDA receptors in the context of long-term potentiation (LTP)?

  • They facilitate calcium influx that is crucial for LTP induction. (correct)
  • They mediate synaptic depression in response to weak stimuli.
  • They decrease synaptic strength during tetanic stimulation.
  • They are solely responsible for the release of neurotransmitters.
  • What is the role of AMPA receptors during the expression of LTP?

  • They both induce and express LTP through calcium signaling.
  • They amplify synaptic strength by allowing more sodium ions to enter the postsynaptic neuron. (correct)
  • They increase the likelihood of neurotransmitter release during low-frequency stimulation.
  • They create new synaptic connections independent of NMDA receptors.
  • What is primarily altered in synapses as a result of LTP induction?

  • The number of synapses present decreases significantly.
  • The structure of the neuron becomes less flexible.
  • There is an increase in neurotransmitter release at the synapse. (correct)
  • Dendritic spines undergo retraction and disappear.
  • Which signaling pathway is primarily involved in the processes that lead to long-term potentiation?

    <p>Calcium signaling pathway. (C)</p> Signup and view all the answers

    Which principle is summarized by the statement 'cells that fire together, wire together'?

    <p>Synaptic connections between simultaneously active neurons are enhanced. (B)</p> Signup and view all the answers

    Which factors are necessary for long-term potentiation (LTP) to occur at synapse A?

    <p>Activity at both synapse A and a weakly stimulated synapse B. (B)</p> Signup and view all the answers

    What characterizes the resting membrane potential in neurons?

    <p>It measures around -70mV. (B)</p> Signup and view all the answers

    What must occur at the NMDA receptor for long-term potentiation (LTP) to be induced?

    <p>Glu must bind to the receptor and the cell must depolarize. (A)</p> Signup and view all the answers

    During depolarization, which of the following occurs?

    <p>Positive ions flow into the cell, reducing negativity. (D)</p> Signup and view all the answers

    How do presynaptic changes contribute to LTP?

    <p>They increase the release of glutamate (Glu). (B)</p> Signup and view all the answers

    Which receptor is primarily involved in the post-synaptic expression of LTP?

    <p>AMPA receptors. (C)</p> Signup and view all the answers

    Which of the following best describes the process of associativity in LTP?

    <p>Weak stimulation at various synapses can lead to strengthening if a strong stimulus activates another synapse. (D)</p> Signup and view all the answers

    What is the role of the field excitatory post-synaptic potential (fEPSP) in measuring synaptic strength?

    <p>fEPSP quantifies the strength of a population of synapses based on extracellular recordings. (C)</p> Signup and view all the answers

    What happens to the Mg2+ block during the induction of LTP?

    <p>It is removed following sufficient depolarization. (C)</p> Signup and view all the answers

    What occurs during the induction phase of LTP?

    <p>Depolarization of the post-synaptic cell is essential and depends on Glu release. (B)</p> Signup and view all the answers

    Which statement best explains the role of calcium (Ca2+) in LTP?

    <p>The influx of Ca2+ initiates the signaling pathways that lead to enhanced synaptic strength. (B)</p> Signup and view all the answers

    What is a key characteristic of Hebbian learning principles as related to NMDA receptors?

    <p>They suggest that changes in synaptic strength depend on the correlation of pre- and post-synaptic activity. (D)</p> Signup and view all the answers

    How is the success of LTP measured according to its standard protocol?

    <p>By calculating the ratio of fEPSP after stimulation to the baseline fEPSP. (A)</p> Signup and view all the answers

    What is a common misconception about tetanus during LTP induction?

    <p>Tetanus is not required during the induction phase for LTP. (D)</p> Signup and view all the answers

    What distinguishes the two pools of AMPAR during LTP expression?

    <p>The surface pool is already present, while the intracellular pool is recruited during LTP. (A)</p> Signup and view all the answers

    What is the consequence when Ca2+ is removed from the synaptic cleft?

    <p>It blocks LTP induction. (B)</p> Signup and view all the answers

    What principle does the phrase 'cells that fire together wire together' illustrate?

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

    Long-term potentiation (LTP) is solely dependent on the stimulation of a single synapse.

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

    What is the term used to describe the persistent increase in synaptic strength following high-frequency stimulation?

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

    The process observed when a weak stimulus applied after a strong stimulus leads to enhanced synaptic activity is known as _____ .

    <p>long-term potentiation</p> Signup and view all the answers

    Match the following components of the medial temporal lobe (MTL) with their primary functions:

    <p>PrC = Objects PHC = Scenes EC = Spatial layouts CA1 = Hippocampal pyramidal cells output</p> Signup and view all the answers

    What is essential for LTP induction to occur?

    <p>Both presynaptic activity and postsynaptic depolarization (A)</p> Signup and view all the answers

    NMDA receptors are involved in both the induction and expression of LTP.

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

    What ion influx is critical for the induction of LTP?

    <p>Calcium (Ca2+)</p> Signup and view all the answers

    The removal of the Mg2+ block from the NMDA receptor is necessary for __________ to occur.

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

    What happens to AMPA receptors when LTP is induced?

    <p>They are recruited from the intracellular pool to increase synaptic strength (B)</p> Signup and view all the answers

    Match the type of antagonist to its function.

    <p>Competitive antagonist = Blocks agonist from binding to the active site Noncompetitive antagonist = Binds to either the active or allosteric site</p> Signup and view all the answers

    What is the consequence of hyperpolarization in terms of LTP?

    <p>It maintains the Mg2+ block, preventing LTP.</p> Signup and view all the answers

    Long-term potentiation (LTP) is an example of Hebbian learning.

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

    What is the primary difference between specificity and associativity in long-term potentiation (LTP)?

    <p>Specificity strengthens only active synapses while associativity strengthens both active and weakly stimulated synapses. (A)</p> Signup and view all the answers

    Long-term potentiation (LTP) can occur without any pre-synaptic neuronal activity.

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

    What does the phosphorylation of Ser831 in AMPAR lead to?

    <p>Increased excitability leading to LTP (D)</p> Signup and view all the answers

    Larger spines in dendritic structures are less stable compared to smaller spines.

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

    What is the typical resting membrane potential in neurons?

    <p>-70 mV</p> Signup and view all the answers

    During depolarization, the ionic composition of the intracellular fluid becomes less ______.

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

    What is the role of CaMK2 in the context of LTP?

    <p>CaMK2 is a memory protein that is required for the expression of LTP and helps in promoting spine growth.</p> Signup and view all the answers

    The process where a strong stimulus leads to strengthening of other synapses is known as __________.

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

    Match the type of potential with its description:

    <p>EPSP = Excitatory postsynaptic potential, causes depolarization IPSP = Inhibitory postsynaptic potential, causes hyperpolarization fEPSP = Field excitatory postsynaptic potential, measures population synaptic strength LTP = Long-term potentiation, a long-lasting increase in synaptic strength</p> Signup and view all the answers

    What is a key requirement for the induction of long-term potentiation (LTP)?

    <p>Depolarization of the post-synaptic cell (C)</p> Signup and view all the answers

    Match the following AMPAR phosphorylation sites with their effects:

    <p>Ser831 = Allows more Na+ influx and supports LTP Ser845 = Tags R for AMPAR removal and reduces excitability</p> Signup and view all the answers

    What impact does low frequency stimulation (LFS) have on LTP?

    <p>Prevents AMPAR recruitment in the first 10 minutes (D)</p> Signup and view all the answers

    The field excitatory post-synaptic potential (fEPSP) is a measure of the strength of a single synapse.

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

    What technique is used to induce long-term potentiation (LTP) in tissue slices?

    <p>Strong stimulation via a stimulating electrode</p> Signup and view all the answers

    Disruption of actin regulation results in larger and more stable synapses.

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

    How does Ca2+ contribute to changes in synapses during LTP?

    <p>Ca2+ activates Calmodulin, which in turn activates CaMK2, leading to synaptic changes.</p> Signup and view all the answers

    Which type of stimulation is associated with the longest duration of long-term potentiation (LTP)?

    <p>Strong stimulation (8 TBS) (B)</p> Signup and view all the answers

    Long-term depression (LTD) is the opposite of long-term potentiation (LTP).

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

    What role does the synaptic tag play in the synaptic tag and capture hypothesis?

    <p>It marks the synapses where strong stimulation occurred to guide mRNA to modify those synapses.</p> Signup and view all the answers

    Low-frequency stimulation (LFS) induces a low fEPSP slope and activates Ser845 to remove ______ from the membrane.

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

    Match the types of stimulation with their corresponding LTP duration:

    <p>Weak stimulation (1 TBS) = Short-lasting LTP Stronger stimulation (4 TBS) = Intermediate LTP Strongest stimulation (8 TBS) = Long-lasting LTP Low Frequency Stimulation (LFS) = Long-term depression</p> Signup and view all the answers

    What effect does the phosphorylation of Ser831 have on AMPAR?

    <p>It allows more Na+ into the cell, making it more excitable. (D)</p> Signup and view all the answers

    Long-term depression (LTD) works in the opposite manner to long-term potentiation (LTP).

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

    What is the role of Ser845 phosphorylation in relation to AMPAR?

    <p>It tags AMPAR for removal from the synapse, reducing excitability.</p> Signup and view all the answers

    Homeostatic plasticity involves neurons opening _____ channels to allow negative ions to enter the cell.

    <p>VG-Cl-</p> Signup and view all the answers

    Match the following processes with their corresponding effects:

    <p>Phosphorylation of Ser831 = Increases excitability and LTP Phosphorylation of Ser845 = Decreases excitability and leads to AMPAR removal Low frequency stimulation (LFS) = Induces LTD Homeostatic plasticity = Maintains neuron excitability</p> Signup and view all the answers

    Flashcards

    Hebbian Plasticity

    Cells that fire together wire together; weak connections between neurons strengthen with repeated activation.

    Long-Term Potentiation (LTP)

    A persistent strengthening of synaptic connections following high-frequency stimulation; a form of synaptic plasticity.

    Tetanic Stimulation

    High-frequency stimulation that induces LTP.

    Synaptic Plasticity

    Changes in synaptic strength, including LTP and LTD resulting from learning or experiences.

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    Hippocampus

    Brain region crucial for declarative memory; part of the medial temporal lobe.

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    Specificity in LTP

    A strong stimulus at one synapse strengthens only that synapse, not others.

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    Associativity in LTP

    Weak stimulation of a synapse can be strengthened when connected to a strongly stimulated synapse.

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    In Vitro LTP Study

    Studying LTP outside the animal in tissue slices (often taken from the hippocampus).

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    fEPSP

    Field excitatory postsynaptic potential; a measure of combined synaptic activity from many nearby neurons.

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    Membrane potential

    The difference in electrical charge between the inside and outside of a cell.

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    Depolarization

    A change in the membrane potential, becoming less negative (more positive) inside.

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    Hyperpolarization

    A change in the membrane potential, becoming more negative inside.

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    LTP Measurement

    LTP is measured by observing a percentage change in fEPSP strength over baseline after a strong stimulation.

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    NMDA Receptor Role

    NMDA receptors are crucial for LTP induction but not for its expression. They act as a "gatekeeper" allowing calcium influx only when both glutamate binds and the postsynaptic cell is sufficiently depolarized.

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    Ca2+ Influx and LTP

    Calcium influx through NMDA receptors during LTP induction is essential for long-term strengthening of the synapse. Blocking calcium prevents LTP.

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    AMPA Receptors in LTP

    AMPA receptors are crucial for LTP expression. They are involved in both the pre-existing surface pool and the intracellular pool, which get mobilized to increase synaptic strength.

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    LTP Induction Requirements

    LTP induction requires both pre- and post-synaptic activity. Glutamate release from the presynaptic neuron is essential, but the postsynaptic neuron must also be sufficiently depolarized to remove the magnesium block from NMDA receptors.

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    LTP and Hebbian Learning

    LTP is strongly linked to Hebbian learning, the idea that "cells that fire together wire together." This suggests that LTP may be a biological mechanism underlying learning and memory.

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    Pre-existing Surface Pool of AMPAR

    A portion of AMPA receptors are already located on the postsynaptic membrane, providing a base level of synaptic strength. Blocking this pool hinders early stages of LTP expression.

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    Intracellular Pool of AMPAR

    A reserve pool of AMPA receptors is stored within the postsynaptic cell. These receptors are mobilized to the surface during LTP induction, contributing to the rapid increase in synaptic strength.

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    Two Ways to Increase AMPARs

    LTP results from two processes: 1) increasing the number of AMPA receptors already on the surface, and 2) recruiting additional AMPA receptors from the intracellular pool.

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    Field EPSP (fEPSP)

    A measure of the strength of a group of synapses, reflecting the sum of extracellular recordings from nearby neurons.

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    Post-synaptic Depolarization for LTP

    A key requirement for LTP is the depolarization of the post-synaptic cell, activated by glutamate released from the pre-synaptic neuron.

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    Glutamate Release & LTP

    For LTP to occur, the presynaptic neuron must release glutamate. This triggers the postsynaptic neuron to become more sensitive to glutamate, strengthening the connection between the neurons.

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    Postsynaptic Depolarization

    The postsynaptic neuron must be sufficiently depolarized, meaning its electrical charge must become more positive. This allows the NMDA receptor to open, allowing calcium ions to flow in.

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    Calcium's Influence

    Calcium ions flowing into the postsynaptic neuron through NMDA receptors are essential for triggering the molecular changes responsible for LTP.

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    AMPA Receptors' Role

    AMPA receptors are located on the postsynaptic membrane and become more abundant during LTP. This increase in AMPA receptors makes the neuron more responsive to glutamate, strengthening the connection.

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    Pre-existing AMPAR Pool

    Some AMPA receptors are already present on the postsynaptic membrane before LTP. Blocking these receptors hinders the early stages of LTP expression.

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    Intracellular AMPAR Pool

    A reserve pool of AMPA receptors is stored inside the postsynaptic neuron. These receptors are recruited to the membrane during LTP, contributing to the rapid increase in synaptic strength.

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    Two Ways to Boost Synaptic Strength

    LTP involves two independent processes to increase synaptic strength: increasing the number of AMPA receptors already on the membrane and recruiting more AMPA receptors from the intracellular pool.

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    Protein Synthesis Inhibition and Memory Consolidation

    Blocking protein synthesis in the hippocampus prevents the formation of long-lasting memories, suggesting that protein synthesis is crucial for memory consolidation.

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    Strength of Stimulation and LTP

    The strength of stimulation determines the type of LTP induced. Weak stimulation leads to short-lasting LTP (LTP1), while stronger stimulation leads to long-lasting LTP (LTP2 and LTP3) involving protein synthesis and gene expression.

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    Synaptic Tag & Capture Hypothesis

    Strong stimulation tags a synapse, marking it for future strengthening. mRNAs carrying proteins needed for LTP are then captured by the tagged synapse.

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    Long-Term Depression (LTD)

    LTD is the opposite of LTP and weakens synaptic connections. It's a way to balance neuron activation and prevent over-excitation.

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    Homeostatic Plasticity

    A mechanism where neurons adjust their excitability to maintain an optimal level of activity. Cells open chloride channels to reduce their responsiveness.

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    Cell Assembly Theory

    A group of neurons that represent a specific concept or memory. They are weakly connected but become strongly linked by repeated stimulation.

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    Role of the MTL in Memory

    The medial temporal lobe (MTL) is crucial for forming new declarative memories, including facts and events. Damage to the MTL, particularly the hippocampus, impairs the ability to create new memories.

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    Tetanic Stimulation and LTP

    Tetanic stimulation is a high-frequency stimulation that induces long-term potentiation (LTP). Following tetanus, synapses become stronger, resulting in a more robust response to future stimuli.

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    LTP Induction and Expression

    LTP induction refers to the process of activating the synapse with high-frequency stimulation. LTP expression refers to the lasting changes in synaptic strength that occur after induction, leading to enhanced transmission.

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    AMPAR Recruitment

    The process of increasing the number of AMPA receptors (AMPARs) at the synapse, leading to stronger synaptic transmission and contributing to LTP.

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    Ser831 Phosphorylation

    Phosphorylation of Ser831 on AMPARs allows more sodium ions to enter the cell, increasing its excitability and contributing to LTP.

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    Ser845 Phosphorylation

    Phosphorylation of Ser845 tags AMPARs for removal from the synapse, reducing excitability and potentially contributing to LTD.

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    CaMK2 Role in LTP

    CaMK2, activated by calcium influx, plays a crucial role in LTP by promoting spine growth, AMPAR recruitment, and strengthening synapses.

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    Spine Size and AMPARs

    Larger spines are more stable and tend to have more AMPARs, contributing to long-lasting LTP.

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    LTP Susceptibility

    LTP is more susceptible to disruption in the first 10 minutes after induction, indicating a time window for stabilizing synaptic changes.

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    Local to Global Changes

    While LTP is initially localized to a single synapse, it can influence other synapses through various mechanisms, leading to global changes in neural networks.

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    What happens when AMPARs switch from GluR1 to GluR2?

    Switching AMPARs from GluR1 to GluR2 removes the magnesium block, always allowing calcium ions to enter the cell, making it more sensitive to glutamate and potentially contributing to LTP.

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    How does Low-Frequency Stimulation (LFS) induce LTD?

    LFS activates Ser845 phosphorylation, leading to removal of AMPARs from the membrane, reducing excitability and effectively weakening the synapse.

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    Study Notes

    Historical Background of Long-Term Potentiation (LTP)

    • Donald Hebb proposed the cell assembly theory, suggesting that groups of neurons can represent memories. Connected neurons strengthen their connections.
    • Hebbian plasticity describes how cells that fire together wire together, strengthening connections.
    • Synaptic plasticity is the idea that memory and learning are represented by changes in synapses, especially LTP and LTD.
    • Patient H.H. with hippocampal damage experienced impaired declarative memory, highlighting the hippocampus's role.

    Neuroanatomy of the Medial Temporal Lobe (MTL)

    • The MTL includes structures like the perirhinal cortex (PrC), parahippocampal cortex (PHC), entorhinal cortex (EC), dentate gyrus (Hipp), CA3/CA1 pyramidal cells, and subiculum complex. These areas are interconnected and crucial for different aspects of memory.
    • These areas are interconnected, and their pathways, such as the perforant path, dentate gyrus, CA3, CA1, and subiculum, process specific types of memories.

    Fundamentals of LTP

    • Long-term potentiation (LTP) is the initial evidence of persistent changes in brain activity caused by manipulation.
    • Tetanic stimulation (high-frequency stimulation) increases synaptic strength, demonstrated using the perforant path/dentate gyrus. A strong stimulus produces high synaptic activity, following a weaker stimulus, resulting in LTP.
    • Weak stimuli produce low synaptic activity. High-frequency stimuli cause high synaptic activity. Applying a weak stimulus after high-frequency stimuli results in potentiation (LTP).

    Specificity and Associativity in LTP

    • LTP is specific to the synapses being stimulated.
    • LTP can be associative, meaning activity at a weak synapse is strengthened when a strong synapse is stimulated.

    Studying LTP in Tissue Slices

    • In vitro techniques allow isolation and study of the hippocampus, maintaining the slice's viability in a chamber with cerebrospinal fluid (CSF).
    • Stimulating and recording electrodes facilitate measuring and monitoring synaptic activity.
    • Extracellular recordings measure field excitatory postsynaptic potentials (fEPSPs). Intracellular recordings measure evoked changes in membrane potential.

    Principles of Electrophysiology

    • Electrophysiology measures the voltage difference between intracellular and extracellular electrodes to determine the membrane potential.
    • Depolarization (EPSP) occurs when positive ions flow into the neuron.
    • Hyperpolarization (IPSP) occurs when positive ions flow out or negative ions flow in.

    Electrophysiology Recordings of Postsynaptic Potentials

    • Field EPSP (fEPSP) measures the sum of postsynaptic potentials from a population of neurons.
    • Slope of the fEPSP reflects the synaptic strength.

    Measuring Long-Term Potentiation

    • Standardized protocols, like establishing a baseline, applying induction stimuli, and monitoring synaptic activity, are used to measure LTP.
    • The dependent variable is the ratio of fEPSP activity during stimulation to the baseline activity, measured as a percentage.

    Induction Phase of LTP

    • Postsynaptic depolarization is essential for LTP.
    • Activating both pre- and post-synaptic neurons is necessary.
    • Activation of NMDA receptors, triggered by depolarization and glutamate release, is important for this phase.
    • Removing the magnesium block from the NMDA receptor is crucial for calcium influx.

    Synaptic Changes Leading to LTP

    • LTP results from presynaptic changes (increased glutamate release) and postsynaptic changes (increased sensitivity to glutamate). Postsynaptic changes are critical for understanding LTP.
    • NMDA receptor activation underlies several LTP mechanisms.

    The NMDA Receptor in LTP

    • NMDA receptors are ionotropic receptors, opening channels when glutamate binds and the cell is sufficiently depolarized to remove a magnesium block.
    • This activation allows calcium influx, which plays a key role in LTP.

    LTP Expression

    • LTP expression involves the insertion of AMPA receptors into the postsynaptic membrane, increasing synaptic strength.

    Two AMPA Pools

    • AMPA receptors exist in pre-existing surface pools and intracellular pools. Intracellular pools are crucial for the increased strength.

    Independent Processes Delivering AMPAR

    • AMPAR are recruited from intracellular pools, moving from lateral diffusion into the postsynaptic density during LTP induction. Motor proteins move intracellular AMPAR to the postsynaptic density.

    How Ca2+ Leads to Synaptic Strength Changes

    • Calcium influx triggers activation of CaMKII/kinases, phosphorylating proteins to alter synapse structure and function, potentially leading to a persistent increase in synaptic strength.
    • Inhibiting protein kinases can block certain LTPs.

    Stability of LTP

    • LTP is susceptible to disruption within the first 10 minutes after stimulation, though later it becomes more stable and resistant to disruption.
    • This reinforces that protein synthesis is important for LTP permanence.

    Local Synaptic Changes Underlying LTP

    • Calcium influx and CaMKII activation lead to AMPA receptor recruitment (either from lateral diffusion or intracellular pools) into the postsynaptic density. This contributes to a strengthened synapse.
    • LTP is dependent on protein synthesis.

    LTP and Different Stimuli

    • Different stimulus frequencies trigger various durations of LTP (LTP1, LTP2, LTP3). This complexity in LTP reflects different physiological and molecular mechanisms involved.

    Long-Term Depression (LTD)

    • LTD, opposite to LTP, is a decrease in synaptic strength. Lower-frequency stimulation or other mechanisms can induce LTD.
    • LTD involves removal of AMPA receptors from the synapse.

    mRNA Transcription & Synaptic Tagging

    • mRNA transcription can specify which synapses are strengthened, suggesting that mRNA tags are crucial for directing mRNA delivery.

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    Explore the historical background and neuroanatomy related to long-term potentiation (LTP) and its significance in memory. This quiz covers key concepts such as Hebbian plasticity, the medial temporal lobe structures, and their roles in memory formation and learning. Test your understanding of these essential neuroscience principles.

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