Excitatory synaptic function- lecture 7

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?

Synaptic plasticity linked to associative learning. Signup and view all the answers

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

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

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

Simultaneous activation of neurons leads to synaptic strengthening. Signup and view all the answers

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

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

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

Through neuronal plasticity including neurogenesis and spiny growth. Signup and view all the answers

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

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

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

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

Which components are necessary for NMDA receptors to activate effectively?

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

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

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

What is the main structural composition of NMDA receptors?

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

Which intracellular processes regulate AMPA receptor activity?

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

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

It prevents NMDA receptors from being activated. Signup and view all the answers

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

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

What is the primary effect of activating Group I mGluRs?

Calcium release from intracellular stores Signup and view all the answers

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

NMDARs have a slower opening and closing time than AMPARs Signup and view all the answers

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

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

Which of the following is an antagonist of AMPARs?

D-AP5 Signup and view all the answers

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

Calcium is essential for synaptic plasticity Signup and view all the answers

Which transmembrane structure is characteristic of metabotropic glutamate receptors?

7 transmembrane domains Signup and view all the answers

What is the effect of AMPAR activation on synaptic transmission?

Fast synaptic transmission Signup and view all the answers

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

IP3 Signup and view all the answers

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

Increased duration of LTP Signup and view all the answers

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

Enhanced AMPAR insertion Signup and view all the answers

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

Postsynaptic calcium influx Signup and view all the answers

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

Removal of AMPARs from the postsynaptic membrane Signup and view all the answers

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

cAMP/PKA pathway Signup and view all the answers

How does the activation of protein kinases contribute to LTP?

They phosphorylate AMPARs and signaling proteins Signup and view all the answers

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

It facilitates calcium binding and kinase activation Signup and view all the answers

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

Reshaping of the actin cytoskeleton Signup and view all the answers

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

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

Which of the following statements about synaptic plasticity is true?

It leads to structural changes at synapses. Signup and view all the answers

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

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

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

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

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

Decreased efficiency of neurotransmitter release. Signup and view all the answers

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

NMDA receptors. Signup and view all the answers

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

Hippocampus. Signup and view all the answers

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

It allows for the adaptation and learning processes. Signup and view all the answers

What type of neurotransmitter is glutamate?

Excitatory neurotransmitter Signup and view all the answers

What type of neurotransmitter is glutamate?

Amino acid Signup and view all the answers

What type of receptors are postsynaptic glutamate receptors?

Both A and B Signup and view all the answers

What role does glutamate play in the brain?

A role in learning, memory Signup and view all the answers

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

Dendritic spines Signup and view all the answers

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

Soma or dendritic shaft Signup and view all the answers

What are dendritic spines?

Small protrusions on the dendrites of neurons that form synapses Signup and view all the answers

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

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

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

They are G-protein coupled receptors. Signup and view all the answers

What are the three types of ionotropic receptors?

NMDA receptors Signup and view all the answers

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

Post-synaptic Signup and view all the answers

What is an AMPA receptor?

A ligand-gated ion channel for glutamate Signup and view all the answers

How many subunits make up the AMPA receptor?

4 Signup and view all the answers

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

GluA1, GluA2, GluA3, GluA4 Signup and view all the answers

What is an NMDA receptor?

A subtype of glutamate receptor involved in synaptic plasticity Signup and view all the answers

What shape do NMDA receptors (NMDARs) take?

Tetrameric structure Signup and view all the answers

What is the kinetics of NMDA receptors (NMDARs)?

Slow activation and deactivation kinetics Signup and view all the answers

What do NMDARs require the binding of to be activated?

Glutamate and Glycine Signup and view all the answers

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

Calcium (Ca²⁺) Signup and view all the answers

Why are NMDARs called voltage-sensitive receptors?

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

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

AMPA/Kainater receptors Signup and view all the answers

Which receptors contribute to the late component of the EPSCs?

NMDA receptors Signup and view all the answers

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

They have a slower opening and closing time Signup and view all the answers

What is a metabotropic glutamate receptor?

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

How many transmembrane domains do metabotropic glutamate receptors have?

7 Signup and view all the answers

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

Group I, Group II, Group III Signup and view all the answers

What are Group I mGluR pathways involved in?

Calcium regulation Signup and view all the answers

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

Phospholipase C pathway Signup and view all the answers

What does phospholipase C (PLC) cleave?

Phosphatidylinositol 4,5-bisphosphate (PIP2) Signup and view all the answers

What is PIP2 cleaved into?

Inositol trisphosphate (IP3) and diacylglycerol (DAG) Signup and view all the answers

What ion does IP3 stimulate the release of?

Calcium (Ca²+) Signup and view all the answers

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

Acts as a secondary messenger activating protein kinase C Signup and view all the answers

What is a homer protein?

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

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

At the presynaptic terminal Signup and view all the answers

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

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

What is excitotoxicity?

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

What is the definition of a Hebbian synapse?

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

What is neuronal plasticity?

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

What is long-term potentiation?

A process that strengthens the connections between neurons in the brain Signup and view all the answers

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

Memory and learning Signup and view all the answers

What is long-term depression?

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

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

Hippocampus Signup and view all the answers

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

All of the above 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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Description

Explore the fascinating world of dendritic spines and their role in excitatory neurons. This quiz covers the dynamics of synaptic inputs and the function of ionotropic glutamate receptors in fast neuronal communication. Test your knowledge on this critical aspect of neuroscience.