Excitatory synaptic function- lecture 7
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Questions and Answers

What is a key characteristic of mGluR activation compared to iGluRs?

  • Both iGluRs and mGluRs activate the same range of channels.
  • iGluRs have broader effects compared to mGluRs.
  • mGluR activation occurs rapidly and has short-lasting effects.
  • mGluR activation has a slower onset and longer lasting effects. (correct)

    • Which role do NMDA receptors play in Hebbian synapses?

  • They act as coincidence detectors to enhance synaptic strength. (correct)
  • They solely regulate the opening of ion channels.
  • They only function during early synaptic development.
  • They exclusively inhibit synaptic activity.

    • In which manner do iGluRs typically function in neuronal processes?

  • They integrate signals from multiple sources simultaneously.
  • They act to continuously modulate synaptic activity.
  • They function as on/off switches at discrete locations. (correct)
  • They alter the overall network plasticity directly.

    • What kind of plasticity does Hebb's postulate primarily relate to?

    <p>Synaptic plasticity linked to associative learning.</p> Signup and view all the answers

    What is a major difference between the effects of iGluRs and mGluRs?

    <p>mGluRs interact with second messenger systems while iGluRs do not.</p> Signup and view all the answers

    What is the concept often summarized by 'neurons that fire together, wire together'?

    <p>Simultaneous activation of neurons leads to synaptic strengthening.</p> Signup and view all the answers

    Which of the following describes a characteristic of AMPA receptors (AMPAR)?

    <p>They mediate fast synaptic transmission in the central nervous system.</p> Signup and view all the answers

    How does plasticity of circuits arise according to the outlined mechanisms?

    <p>Through neuronal plasticity including neurogenesis and spiny growth.</p> Signup and view all the answers

    What is the role of calcium flux through NMDA receptors in neuronal function?

    <p>It serves as a critical factor in synaptic plasticity, influencing learning and memory.</p> Signup and view all the answers

    What characterizes the kinetics of AMPA receptors compared to NMDA receptors?

    <p>AMPARs open and close quickly, providing a fast response in synaptic transmission.</p> Signup and view all the answers

    Which components are necessary for NMDA receptors to activate effectively?

    <p>Both glutamate and a co-agonist, along with sufficient membrane depolarization.</p> Signup and view all the answers

    How do AMPA receptors contribute to synaptic transmission compared to NMDA receptors?

    <p>They generate the initial fast component of excitatory postsynaptic currents (EPSCs).</p> Signup and view all the answers

    What is the main structural composition of NMDA receptors?

    <p>They consist of a tetramer formed from specific combinations of three types of subunits.</p> Signup and view all the answers

    Which intracellular processes regulate AMPA receptor activity?

    <p>Regulation occurs via messenger cascades involving PKA, PKC, and CaMKII.</p> Signup and view all the answers

    What characterizes the magnesium block in NMDA receptors at resting membrane potential?

    <p>It prevents NMDA receptors from being activated.</p> Signup and view all the answers

    In what way do dendritic spines input into the function of excitatory neurons?

    <p>They act as the primary sites for synaptic inputs via presynaptic axons.</p> Signup and view all the answers

    What is the primary effect of activating Group I mGluRs?

    <p>Calcium release from intracellular stores</p> Signup and view all the answers

    What distinguishes the opening and closing times of NMDARs from AMPARs?

    <p>NMDARs have a slower opening and closing time than AMPARs</p> Signup and view all the answers

    Which molecule is generated when PIP2 is cleaved by phospholipase C (PLC)?

    <p>Inositol-1,4,5-triphosphate (IP3)</p> Signup and view all the answers

    Which of the following is an antagonist of AMPARs?

    <p>D-AP5</p> Signup and view all the answers

    What role does calcium play in synaptic function following the activation of Group I mGluRs?

    <p>Calcium is essential for synaptic plasticity</p> Signup and view all the answers

    Which transmembrane structure is characteristic of metabotropic glutamate receptors?

    <p>7 transmembrane domains</p> Signup and view all the answers

    What is the effect of AMPAR activation on synaptic transmission?

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

    Which substance diffuses to the cytoplasm after Group I mGluR activation?

    <p>IP3</p> Signup and view all the answers

    What results from the self-phosphorylation of CaMKaII during the induction of LTP?

    <p>Increased duration of LTP</p> Signup and view all the answers

    What is a critical effect of Ca2+ influx through NMDARs in the context of LTP?

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

    Which of the following is a mechanism involved in the induction of LTP at Schaffer collateral-CA1 synapses?

    <p>Postsynaptic calcium influx</p> Signup and view all the answers

    Which process leads to long-term depression (LTD) at the synapse?

    <p>Removal of AMPARs from the postsynaptic membrane</p> Signup and view all the answers

    Which signaling pathway is primarily associated with presynaptic calcium influx in LTP at mossy fiber-CA3 synapses?

    <p>cAMP/PKA pathway</p> Signup and view all the answers

    How does the activation of protein kinases contribute to LTP?

    <p>They phosphorylate AMPARs and signaling proteins</p> Signup and view all the answers

    What role does calmodulin (CaM) play in the context of CaMKaII activation during LTP?

    <p>It facilitates calcium binding and kinase activation</p> Signup and view all the answers

    What determines the growth or shrinkage of the synaptic spine during LTP and LTD?

    <p>Reshaping of the actin cytoskeleton</p> Signup and view all the answers

    What is the role of AMPA receptors in the process of long-term potentiation (LTP)?

    <p>They facilitate the activation of NMDA receptors after partial depolarization.</p> Signup and view all the answers

    Which of the following statements about synaptic plasticity is true?

    <p>It leads to structural changes at synapses.</p> Signup and view all the answers

    What must happen before NMDA receptors can respond during LTP in the hippocampus?

    <p>A sufficient number of AMPA receptors must be stimulated.</p> Signup and view all the answers

    What is primarily altered during the mechanisms of long-term potentiation (LTP)?

    <p>The strength of connections between axon terminals and dendritic spines is increased.</p> Signup and view all the answers

    Which of the following mechanisms is most closely associated with long-term depression (LTD)?

    <p>Decreased efficiency of neurotransmitter release.</p> Signup and view all the answers

    Which ionotropic glutamate receptor does not respond until enough AMPA receptors are stimulated?

    <p>NMDA receptors.</p> Signup and view all the answers

    In which part of the brain is long-term potentiation (LTP) primarily studied?

    <p>Hippocampus.</p> Signup and view all the answers

    What is a key function of synaptic plasticity in the nervous system?

    <p>It allows for the adaptation and learning processes.</p> Signup and view all the answers

    What type of neurotransmitter is glutamate?

    <p>Excitatory neurotransmitter</p> Signup and view all the answers

    What type of neurotransmitter is glutamate?

    <p>Amino acid</p> Signup and view all the answers

    What type of receptors are postsynaptic glutamate receptors?

    <p>Both A and B</p> Signup and view all the answers

    What role does glutamate play in the brain?

    <p>A role in learning, memory</p> Signup and view all the answers

    When the postsynaptic neuron is excitatory, where is the glutamatergic synapse typically found on the excitatory cell?

    <p>Dendritic spines</p> Signup and view all the answers

    When the postsynaptic neurons are inhibitory, where are the glutamatergic synapses typically found?

    <p>Soma or dendritic shaft</p> Signup and view all the answers

    What are dendritic spines?

    <p>Small protrusions on the dendrites of neurons that form synapses</p> Signup and view all the answers

    What are the properties of ionotropic receptors? (Select all that apply)

    <p>They mediate fast synaptic transmission, ions flow in/out of neuron.</p> Signup and view all the answers

    What are the characteristics of metabotropic receptors? (Select all that apply)

    <p>They are G-protein coupled receptors.</p> Signup and view all the answers

    What are the three types of ionotropic receptors?

    <p>NMDA receptors</p> Signup and view all the answers

    Are NMDARs, AMPARs, and Kainate receptors post-synaptic or pre-synaptic?

    <p>Post-synaptic</p> Signup and view all the answers

    What is an AMPA receptor?

    <p>A ligand-gated ion channel for glutamate</p> Signup and view all the answers

    How many subunits make up the AMPA receptor?

    <p>4</p> Signup and view all the answers

    What are the subunits of the AMPA receptor (AMPAR)?

    <p>GluA1, GluA2, GluA3, GluA4</p> Signup and view all the answers

    What is an NMDA receptor?

    <p>A subtype of glutamate receptor involved in synaptic plasticity</p> Signup and view all the answers

    What shape do NMDA receptors (NMDARs) take?

    <p>Tetrameric structure</p> Signup and view all the answers

    What is the kinetics of NMDA receptors (NMDARs)?

    <p>Slow activation and deactivation kinetics</p> Signup and view all the answers

    What do NMDARs require the binding of to be activated?

    <p>Glutamate and Glycine</p> Signup and view all the answers

    What ions do NMDARs primarily (N-methyl-D-aspartate receptors) allow to enter a neuron?

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

    Why are NMDARs called voltage-sensitive receptors?

    <p>They open only when the membrane potential is depolarized, causing Mg to dissociate which usually blocks the channel.</p> Signup and view all the answers

    Which type of receptors generate the large and early component of EPSCs?

    <p>AMPA/Kainater receptors</p> Signup and view all the answers

    Which receptors contribute to the late component of the EPSCs?

    <p>NMDA receptors</p> Signup and view all the answers

    Why do NMDA receptors contribute to the late component of the excitatory postsynaptic currents (EPSCs)?

    <p>They have a slower opening and closing time</p> Signup and view all the answers

    What is a metabotropic glutamate receptor?

    <p>A receptor that activates intracellular signaling pathways through G-proteins.</p> Signup and view all the answers

    How many transmembrane domains do metabotropic glutamate receptors have?

    <p>7</p> Signup and view all the answers

    What are the three functional groups of metabotropic glutamate receptors (mGluRs)?

    <p>Group I, Group II, Group III</p> Signup and view all the answers

    What are Group I mGluR pathways involved in?

    <p>Calcium regulation</p> Signup and view all the answers

    Which of the following are signaling cascades involved in Group I mGluR pathways?

    <p>Phospholipase C pathway</p> Signup and view all the answers

    What does phospholipase C (PLC) cleave?

    <p>Phosphatidylinositol 4,5-bisphosphate (PIP2)</p> Signup and view all the answers

    What is PIP2 cleaved into?

    <p>Inositol trisphosphate (IP3) and diacylglycerol (DAG)</p> Signup and view all the answers

    What ion does IP3 stimulate the release of?

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

    What is the primary function of diacylglycerol (DAG) in cellular signaling?

    <p>Acts as a secondary messenger activating protein kinase C</p> Signup and view all the answers

    What is a homer protein?

    <p>A protein involved in the trafficking mGluRs into and out of synapses</p> Signup and view all the answers

    Where are group 2/3 mGluRs predominantly found on a neuron?

    <p>At the presynaptic terminal</p> Signup and view all the answers

    How do group 2 and 3 mGluRs function in synaptic signaling?

    <p>Pre-synaptic terminals reducing the amount of glutamate release from terminals</p> Signup and view all the answers

    What is excitotoxicity?

    <p>A process in which neurons are damaged and killed by excessive stimulation by neurotransmitters such as glutamate.</p> Signup and view all the answers

    What is the definition of a Hebbian synapse?

    <p>A synapse that strengthens connections between neurons that are actively involved in the same process.</p> Signup and view all the answers

    What is neuronal plasticity?

    <p>The ability of neurons to change their connections and behavior in response to experience</p> Signup and view all the answers

    What is long-term potentiation?

    <p>A process that strengthens the connections between neurons in the brain</p> Signup and view all the answers

    What functions is Long-Term Potentiation (LTP) associated with?

    <p>Memory and learning</p> Signup and view all the answers

    What is long-term depression?

    <p>A decrease in the efficacy of synaptic transmission that lasts for hours or longer after stimulation.</p> Signup and view all the answers

    What area of the brain is key in memory and learning?

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

    In which regions of the hippocampus does long-term potentiation (LTP) occur?

    <p>All of the above</p> Signup and view all the answers

    Study Notes

    Dendritic Spines and Synaptic Inputs

    • Dendrites of excitatory neurons have dynamic dendritic spines that receive synaptic inputs from presynaptic axons.
    • Spines exhibit plasticity, allowing them to adapt structurally and functionally.

    Glutamate Receptors Overview

    • Two major types:
      • Ionotropic receptors (iGluRs): Enable fast transmission; ions flow in/out; milliseconds for responses.
      • Metabotropic receptors (mGluRs): Mediate slow transmission; activate intracellular signaling cascades; seconds for responses.

    Ionotropic Glutamate Receptors (iGluRs)

    • Types include AMPA receptors (AMPARs), NMDA receptors (NMDARs), and Kainate receptors (KARs).
    • AMPARs and NMDARs are co-localized at glutamatergic synapses, responsible for fast synaptic transmission.
    • NMDARs and AMPARs can be located both synaptic and extrasynaptic, and can function as autoreceptors or postsynaptic receptors.

    AMPA Receptors (AMPARs)

    • Rapid opening and closing, crucial for fast excitatory synaptic transmission within the CNS.
    • Permeable to sodium, potassium, and some calcium.
    • Composed of four subunits (GluA1, GluA2, GluA3, GluA4) and regulated by kinases such as PKA, PKC, and CaMKII.

    NMDA Receptors (NMDARs)

    • Function as tetrameric receptors with three subunit types, requiring glutamate and glycine binding for activation.
    • Allow calcium, sodium, and potassium entry; slow kinetics compared to AMPARs.
    • Ligand- and voltage-sensitive; magnesium ions block permeability at resting potential, relieved by depolarization.

    Coincidence Detection and Synaptic Plasticity

    • NMDARs require simultaneous presence of glutamate, glycine, and depolarization for activation.
    • Calcium influx through NMDARs is vital for synaptic plasticity and plays a key role in learning and memory.

    Kinetics of NMDA and AMPA Receptors

    • AMPARs produce a rapid early response while NMDARs contribute to a slower, later response during synaptic transmission.
    • NMDARs exhibit slower activation/deactivation compared to AMPARs, influencing synaptic response dynamics.

    Metabotropic Glutamate Receptors (mGluRs)

    • Single polypeptide proteins with seven transmembrane domains, linking glutamate binding to G-protein signaling cascades.
    • Eight subtypes categorized into three functional groups; activation induces changes in synaptic activity.

    Group I mGluR Pathways

    • Activation leads to phospholipase C (PLC) activity, producing inositol triphosphate (IP3) and diacylglycerol (DAG).
    • Increase in intracellular calcium through ER release, influencing synaptic efficacy and plasticity.

    Hebbian Plasticity

    • Concept introduced by Donald Hebb: "Neurons that fire together, wire together."
    • Repeated stimulation strengthens synaptic connections aiding in memory storage.
    • NMDA receptors facilitate Hebbian behavior through their voltage-dependent characteristics and calcium permeability.

    Long-Term Potentiation (LTP) and Long-Term Depression (LTD)

    • LTP involves the insertion of AMPARs into the postsynaptic membrane enhancing synaptic strength.
    • LTD is characterized by the removal of AMPARs, reducing synaptic strength.
    • Both forms of plasticity are essential for learning and memory and involve structural changes in dendritic spines.

    Role of Calcium in LTP

    • Calcium influx activates kinases (e.g., CaMKII, PKC), leading to AMPAR phosphorylation and increased synaptic efficacy.
    • CaMKII activation is crucial for LTP maintenance due to its self-phosphorylation ability.

    Synaptic Plasticity Measurement

    • LTP occurs in various hippocampal regions, notably CA1, which hosts both NMDARs and AMPARs.
    • Glutamate initially activates AMPARs; NMDARs become active upon partial depolarization following AMPAR stimulation.

    Hippocampus as a Learning Hub

    • The hippocampus is pivotal for memory formation and learning, facilitating mechanisms like LTP relevant to synaptic plasticity.

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