Neurotransmitter Release and Synaptic Transmission

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Questions and Answers

What is the primary role of $Ca^{++}$ ions in the process of neurotransmitter release at the synapse?

  • To initiate the synthesis of neurotransmitters within the pre-synaptic terminal.
  • To promote the exocytosis of neurotransmitter-containing vesicles from the pre-synaptic terminal. (correct)
  • To bind to ligand-gated channels on the post-synaptic membrane.
  • To directly alter the membrane potential of the post-synaptic neuron.

How does measuring the capacitance of the terminal membrane physiologically indicate changes during synaptic transmission?

  • Increased capacitance reflects endocytosis, as membrane area decreases.
  • Increased capacitance reflects exocytosis, as membrane area increases. (correct)
  • Decreased capacitance reflects exocytosis, as membrane area increases.
  • Capacitance measurements are indicative of ion channel conductance, not membrane area changes.

Which of the following is directly involved in regulating neurotransmitter release at the synapse?

  • Acetylcholinesterase in the synaptic cleft
  • Voltage-gated Sodium ($Na^+$) channels
  • SNARE complex proteins (correct)
  • Ligand-gated ion channels on the post-synaptic membrane

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder that affects chemical synaptic transmission. Which component is primarily targeted in LEMS?

<p>Voltage-gated Calcium ($Ca^{++}$) channels in the pre-synaptic terminal (C)</p> Signup and view all the answers

What is the immediate consequence of $Ca^{++}$ influx into the pre-synaptic terminal following the arrival of an action potential?

<p>Promotion of exocytosis of neurotransmitter from synaptic vesicles. (C)</p> Signup and view all the answers

Miniature end plate potentials (mEPPs) are distinguished from end plate potentials (EPPs) at the neuromuscular junction primarily by their:

<p>spontaneous occurrence in the absence of presynaptic action potentials. (D)</p> Signup and view all the answers

The experiment using jellyfish aequorin protein at the squid giant synapse demonstrated that:

<p>an increase in presynaptic calcium concentration is necessary for neurotransmitter release. (B)</p> Signup and view all the answers

The 'vesicular hypothesis' in the context of neuromuscular junction transmission proposes that:

<p>mEPPs represent the postsynaptic response to the release of neurotransmitter from a single vesicle. (D)</p> Signup and view all the answers

In the sequence of events leading to neurotransmitter release, the opening of voltage-gated calcium channels in the presynaptic terminal is directly triggered by:

<p>the depolarization of the presynaptic terminal due to the arrival of an action potential. (C)</p> Signup and view all the answers

Why is the influx of calcium ions ($Ca^{++}$) rather than sodium ions ($Na^{+}$) critical for initiating neurotransmitter release at the presynaptic terminal?

<p>Calcium ion influx causes a prolonged inward current ($I_{Ca}$) and a very positive equilibrium potential ($E_{Ca}$), facilitating depolarization and exocytosis. (B)</p> Signup and view all the answers

What is the approximate synaptic cleft distance that distinguishes a chemical synapse from an electrical synapse?

<p>200 nm for chemical, 20 nm for electrical (B)</p> Signup and view all the answers

Which feature is essential for signal transmission across a chemical synapse but not across an electrical synapse?

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

Regarding the speed of synaptic transmission, how do electrical synapses compare to chemical synapses?

<p>Electrical synapses are significantly faster due to direct electrical flow. (C)</p> Signup and view all the answers

Which of the following neurotransmitters is classified as inhibitory and prevalent in CNS type II synapses?

<p>Gamma amino butyric acid (GABA) (A)</p> Signup and view all the answers

What anatomical structure is specifically referred to as the neuromuscular junction (NMJ)?

<p>The end plate region where a motor neuron axon terminal synapses with a muscle fiber (C)</p> Signup and view all the answers

In immunochemistry studies of synapses, what role do spider toxin and cobra toxin play in identifying synaptic components?

<p>Spider toxin targets pre-synaptic Ca channels, and cobra toxin targets post-synaptic Ach receptors. (A)</p> Signup and view all the answers

Which of the following microscopic techniques is most directly associated with the observation of 'omega figures' as evidence for exocytosis during neurotransmission?

<p>Transmission electron microscopy (TEM) (D)</p> Signup and view all the answers

The observation of vesicle and membrane fusion during nerve stimulation under electron microscopy primarily provides evidence for which synaptic process?

<p>Exocytosis (D)</p> Signup and view all the answers

Opening of chloride (Cl-) channels in a neuron typically leads to:

<p>Inhibition of excitatory postsynaptic potentials. (B)</p> Signup and view all the answers

Neuropeptides differ from classical neurotransmitters like GABA and glycine in their:

<p>Site of synthesis within the neuron. (A)</p> Signup and view all the answers

Selective Serotonin Reuptake Inhibitors (SSRIs) primarily exert their therapeutic effects by:

<p>Prolonging the presence of serotonin in the synapse. (B)</p> Signup and view all the answers

Which of the following biogenic amines is derived from the amino acid tryptophan?

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

What is the primary characteristic of neurotransmission mediated by ligand-gated ionotropic receptors?

<p>Rapid postsynaptic responses due to direct ion flux (C)</p> Signup and view all the answers

Monoamine oxidase inhibitors (MAOIs) increase the synaptic concentration of certain neurotransmitters by:

<p>Inhibiting the enzymes responsible for their breakdown. (C)</p> Signup and view all the answers

An excitatory postsynaptic potential (EPSP) is primarily caused by the:

<p>Influx of sodium ions ($Na^+$) into the postsynaptic neuron (B)</p> Signup and view all the answers

Inhibitory postsynaptic potentials (IPSPs) are typically generated by the opening of channels selective for:

<p>Potassium ($K^+$) or chloride ions ($Cl^-$) (B)</p> Signup and view all the answers

Which enzyme is responsible for the synthesis of acetylcholine (ACh) in the nerve terminal?

<p>Choline acetyltransferase (ChaT) (C)</p> Signup and view all the answers

Acetylcholinesterase (AChE) inhibitors, such as certain pesticides and nerve gases, lead to:

<p>Prolonged presence of acetylcholine in the synaptic cleft (B)</p> Signup and view all the answers

What distinguishes the NMDA receptor from the AMPA/kainate receptor in glutamatergic neurotransmission?

<p>NMDA receptors require both glutamate binding and membrane depolarization to open, unlike AMPA/kainate receptors. (C)</p> Signup and view all the answers

The GABA$_A$ receptor, a major inhibitory receptor in the CNS, is directly associated with a:

<p>Chloride ($Cl^-$) channel (B)</p> Signup and view all the answers

In neural circuits, inhibitory postsynaptic potentials (IPSPs) primarily function to:

<p>Sculpt or terminate ongoing neural activity by reducing neuronal excitability. (B)</p> Signup and view all the answers

Flashcards

Synaptic Transmission

Communication between neurons or between a neuron and a target cell, involving the release of chemical messengers called neurotransmitters.

Chemical Synapse

A type of synaptic transmission that uses chemical messengers called neurotransmitters to transmit signals across the synaptic cleft.

Electrical Synapse

A type of synaptic transmission that allows direct electrical flow between cells through specialized protein channels called connexons.

Neuromuscular Junction (NMJ)

A specialized type of chemical synapse found at the junction between a motor neuron and a muscle fiber.

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Post-synaptic Receptor

A protein embedded in the postsynaptic membrane that binds to a specific neurotransmitter, causing a change in the postsynaptic cell's membrane potential.

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Glutamate

An excitatory neurotransmitter that opens channels for sodium ions to enter the postsynaptic cell, leading to depolarization and increased likelihood of an action potential.

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GABA

An inhibitory neurotransmitter that opens channels for chloride ions to enter the postsynaptic cell, leading to hyperpolarization and decreased likelihood of an action potential.

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Exocytosis

The process by which neurotransmitters are released from the presynaptic terminal into the synaptic cleft.

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Miniature End Plate Potential (mEPP)

A miniature end plate potential (mEPP) is a small, graded potential that occurs at the neuromuscular junction (NMJ) in the absence of a presynaptic action potential. It represents the release of a single vesicle of neurotransmitter from the presynaptic terminal.

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Vesicular Hypothesis

The vesicular hypothesis states that mEPPs are caused by the release of a single vesicle of neurotransmitter from the presynaptic terminal. This is supported by the observation that mEPPs are quantized, meaning they occur in discrete units, and that their amplitude is proportional to the number of vesicles released.

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End Plate Potential (EPP)

The end plate potential (EPP) is a large, graded potential that occurs at the NMJ when multiple vesicles of neurotransmitter are released from the presynaptic terminal. EPPs are the NMJ equivalent of excitatory postsynaptic potentials (EPSPs) in neurons and are responsible for muscle fiber contraction.

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Calcium's Role in Neurotransmitter Release

Calcium ions (Ca++) play a crucial role in neurotransmitter release. Presynaptic depolarization triggers the opening of voltage-gated calcium channels, allowing Ca++ to enter the presynaptic terminal. This influx of Ca++ initiates the fusion of synaptic vesicles with the presynaptic membrane, releasing neurotransmitter into the synaptic cleft.

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Voltage-gated Calcium Channels

Calcium channels are voltage-sensitive proteins embedded in the presynaptic terminal membrane. Their opening is triggered by a change in the membrane potential, allowing Ca++ ions to flow into the terminal. This influx of Ca++ plays a critical role in the process of neurotransmitter release.

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Why is a large calcium spike needed for exocytosis?

Calcium ions (Ca++) are essential for exocytosis, the process of releasing neurotransmitters from the presynaptic neuron. A significant increase in intracellular calcium concentration ([Ca]INT) is required for exocytosis to occur, not just a brief interaction with the cell membrane.

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What is the SNARE complex?

The SNARE complex is a group of proteins that facilitate the fusion of synaptic vesicles with the presynaptic membrane, allowing for neurotransmitter release. This complex involves proteins from both the vesicle and the membrane, ensuring proper docking and fusion.

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How is capacitance related to exocytosis and endocytosis?

The capacitance of the presynaptic terminal membrane - a measure of its ability to store electrical charge - increases during exocytosis due to the addition of membrane as vesicles fuse. Conversely, endocytosis, the process of taking in vesicles, decreases capacitance as membrane area decreases.

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How does Botulinum toxin work?

Botulinum toxin blocks the release of acetylcholine at neuromuscular junctions by interfering with the SNARE complex. This action prevents the proper fusion of vesicles containing acetylcholine, leading to muscle paralysis. This toxin is highly potent and can be fatal.

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What is Lambert-Eaton Myasthenic Syndrome?

Lambert-Eaton Myasthenic Syndrome (LEMS) is an autoimmune disease in which the body's immune system attacks the voltage-gated calcium channels on the presynaptic neurons. This leads to a decrease in calcium influx, subsequently reducing neurotransmitter release, resulting in muscle weakness.

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Inhibitory Cl- Channels

Cl- channels that open in response to GABA or glycine neurotransmitters, allowing Cl- ions to flow into the neuron, making it more negative and less likely to fire an action potential.

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GABA & Glycine as Inhibitory Neurotransmitters

A type of neurotransmitter that binds to ionotropic receptors, opening channels for chloride ions (Cl-) to flow into the neuron, causing hyperpolarization and inhibiting the neuron from firing an action potential.

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Shunting Inhibition

When inhibitory neurotransmitters like GABA and glycine cause an influx of negative ions, they effectively 'shunt' away excitatory currents, reducing the likelihood of the neuron firing.

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Neuropeptides

Short proteins synthesized in the cell body and transported to the axon terminal. They can act as neurotransmitters for fast signaling or neuromodulators for slower, longer-lasting effects.

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Biogenic Amines

A family of neurotransmitters with different types, including catecholamines (dopamine, epinephrine, norepinephrine), indole-amines (serotonin), and imidazole-amines (histamine). They play diverse and important roles in the nervous system.

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Ionotropic Receptor

A type of neurotransmitter receptor that is directly linked to an ion channel, allowing ions to flow across the cell membrane upon ligand binding.

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Postsynaptic Potential (PSP)

A short-lived, localized change in membrane potential that occurs at the postsynaptic membrane in response to neurotransmitter binding.

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Acetylcholine (Ach)

The neurotransmitter responsible for signaling at the neuromuscular junction, leading to muscle contraction.

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Choline Acetyltransferase (ChAT)

The enzyme that synthesizes acetylcholine (Ach) from choline and acetyl-CoA in the presynaptic terminal.

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Acetylcholinesterase (AchE)

The enzyme that breaks down acetylcholine (Ach) in the synaptic cleft. This action helps terminate the synaptic transmission.

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AMPA/Kainate Receptor

A type of ionotropic receptor that is gated by the binding of glutamate and opens channels for sodium ions, leading to membrane depolarization and excitation.

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NMDA Receptor

A type of ionotropic receptor that is gated by both glutamate and a positive membrane potential, opening channels for calcium ions. This receptor plays a crucial role in learning and memory.

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GABA (Gamma-Aminobutyric Acid)

The primary inhibitory neurotransmitter in the central nervous system (CNS). It binds to GABA receptors, opening chloride channels and causing hyperpolarization.

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Study Notes

Synaptic Transmission

  • Synaptic transmission involves chemical and electrical mechanisms.
  • Morphological studies examine the structure of synapses.
  • Physiological studies analyze synaptic function.

Neurotransmitters

  • Acetylcholine (ACh), amino acids (like glutamate and GABA), amines (like dopamine and serotonin), and peptides are neurotransmitters.
  • Neurotransmitters are involved in both excitatory and inhibitory actions.
  • Uptake and termination of neurotransmitters are important processes.
  • Pharmacology plays a role in understanding and manipulating neurotransmitters.

Chemical Synapses

  • Chemical synapses use neurotransmitters to transmit signals across a 200 nm gap.
  • Neurotransmitters bind to receptors on the postsynaptic membrane.
  • Examples include neuromuscular junctions (NMJ).

Electrical Synapses

  • Electrical synapses transmit signals directly across a 20 nm gap.
  • Specialized channels (connexons) connect pre- and postsynaptic membranes.
  • Electrical synapses are faster than chemical synapses.

Synaptic Morphology

  • The neuromuscular junction (NMJ) is a specific synapse.
  • Immunochemistry is used to identify pre- and post-synaptic membrane proteins.
  • Pre-synaptic terminals contain calcium channels, while post-synaptic membranes have receptors for neurotransmitters.

Exocytosis During Neurotransmission

  • Torpedo electric rays are used to study exocytosis.
  • Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) are used to observe vesicle/membrane interactions.
  • Freeze-fracture techniques help visualize membrane structures.

Physiological View of Exocytosis

  • Miniature end-plate potentials (mEPPs) are graded potentials.
  • Miniature End Plate Potentials (mEPPs) appear in the absence of pre-synaptic activity.
  • mEPPs reflect vesicle release at the neuromuscular junction (NMJ).

Jellyfish Aequorin Protein

  • Jellyfish aequorin protein is a bioluminescent calcium indicator.
  • It is used to measure pre-synaptic calcium during depolarization.
  • Studies use the squid giant synapse method.

Ca++ Channels Regulate NT Release

  • The arrival of a Na+/K+ action potential causes depolarization.
  • Voltage-gated calcium channels open in the pre-synaptic terminal.
  • Increased calcium permeability depolarizes the membrane (ECa).
  • Inward calcium current (Ica) is prolonged.

Exocytosis and Endocytosis

  • Physiological measures of membrane capacitance are used to study exocytosis and endocytosis.
  • 'Kiss-and-run' exocytosis is distinct from bulk exocytosis.
  • Capacitance decreases during endocytosis.

SNARE Complex

  • SNARE complex proteins regulate synaptic vesicle and membrane fusion.

Toxins Affecting Ca++ Mechanism

  • Botulinum toxins and tetanus toxins affect the SNARE complex.

Neurotransmitters. 1. Acetylcholine

  • Choline acetyltransferase (ChAT) is involved in ACh synthesis.
  • Acetylcholinesterase (AChE) breaks down ACh in the synaptic cleft.
  • Acetylcholine plays important roles in the nervous system.
  • Cholinergic synapses target numerous receptors and affect the nervous system.
  • Cholinergic pathways use ACh as their crucial neurotransmitter.

Glutamate

  • Glutamate is the major excitatory neurotransmitter.
  • AMPA/kainate receptors and NMDA receptors are involved in glutamate transmission.

Glycine and GABA

  • Glycine and GABA are major inhibitory neurotransmitters.
  • Their associated receptors have chloride channels.
  • GABA and Glycine create inhibitory post-synaptic potentials (IPSPs).

Neuropeptides

  • Neuropeptides are short proteins synthesized in the cell body.
  • They function as both transmitters and modulators.
  • They often act in conjunction with classical neurotransmitters.

Biogenic Amines

  • Biogenic amines are derived from aromatic amino acids.
  • Dopamine, norepinephrine, epinephrine, serotonin, and histamine are examples.

Uptake and Synthesis of NTs

  • Diffusion terminates neurotransmitter signals.
  • Glial cells are involved in reuptake.
  • Enzymes and transporters are crucial for neurotransmitter synthesis and breakdown.

Enzymatic Breakdown of Amines

  • Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are enzymes that break down amine neurotransmitters.

Pharmacological Intervention at Aminergic Synapses

  • Various drugs target neurotransmitters and their regulatory systems, such as tyrosine hydroxylase, L-DOPA, reserpine, propranolol, cocaine, SSRIs, and MAO inhibitors.

Myasthenia Gravis

  • Myasthenia gravis is an autoimmune disease.
  • The immune system attacks acetylcholine receptors.
  • Symptoms include muscle weakness.

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