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Related Concept Videos

Chemical Synapses01:26

Chemical Synapses

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Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
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Chemical Synapses01:26

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Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
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Neurochemical Transmission: Sites of Drug Action01:26

Neurochemical Transmission: Sites of Drug Action

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Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...
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Electrical Synapses01:28

Electrical Synapses

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Electrical synapses found in all nervous systems play important and unique roles. In these synapses, the presynaptic and postsynaptic membranes are very close together (3.5 nm) and are actually physically connected by channel proteins forming gap junctions.
Gap junctions allow the current to pass directly from one cell to the next. In contrast, in the chemical synapse, the neurotransmitters carry the information through the synaptic cleft from one neuron to the next. They consist of two...
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Overview of Synapses01:25

Overview of Synapses

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A synapse is a specialized structure where two neurons connect, allowing them to pass an electrical or chemical signal to another neuron. It is the point of communication between neurons. The term "synapse" is derived from the Greek word "synapsis," which means "conjunction." The entire process of neural communication revolves around the synapse. When activated, a neuron releases chemicals known as neurotransmitters into the synapse. These neurotransmitters cross the synapse and bind to...
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The Synapse02:47

The Synapse

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Neurons communicate with one another by passing on their electrical signals to other neurons. A synapse is the location where two neurons meet to exchange signals. At the synapse, the neuron that sends the signal is called the presynaptic cell, while the neuron that receives the message is called the postsynaptic cell. Note that most neurons can be both presynaptic and postsynaptic, as they both transmit and receive information.
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Presynaptically Silent Synapses Studied with Light Microscopy
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Structural elements that underlie Doc2β function during asynchronous synaptic transmission.

Renhao Xue1, Jon D Gaffaney1, Edwin R Chapman2

  • 1Department of Neuroscience, University of Wisconsin, Madison, WI 53706; and Howard Hughes Medical Institute, University of Wisconsin, Madison, WI 53706.

Proceedings of the National Academy of Sciences of the United States of America
|July 22, 2015
PubMed
Summary
This summary is machine-generated.

Double C2-like domain-containing proteins alpha and beta (Doc2α and Doc2β) are Ca(2+) sensors for neurotransmitter release. Key Ca(2+) binding sites in Doc2β

Keywords:
C2-domainCa2+ sensorDoc2βasynchronous synaptic transmissionsynaptotagmin 1

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Double C2-like domain-containing proteins alpha and beta (Doc2α and Doc2β) are implicated as Ca(2+) sensors in neurotransmitter release.
  • Their precise role in synaptic transmission, particularly the slow phase, requires detailed molecular dissection.

Purpose of the Study:

  • To systematically identify the critical Ca(2+) binding residues in the Doc2β isoform.
  • To elucidate the functional significance of these residues in Ca(2+)-dependent plasma membrane translocation and neurotransmitter release.

Main Methods:

  • Site-directed mutagenesis of Doc2β to neutralize Ca(2+) coordinating residues.
  • Biochemical assays to assess Ca(2+)-dependent membrane translocation.
  • Electrophysiological recordings in neurons to measure neurotransmitter release kinetics.
  • Construction of synaptotagmin 1-Doc2β chimeras.

Main Results:

  • Ca(2+) ligands in the C2A domain were largely dispensable for translocation, except for D220, which mediated constitutive translocation when neutralized.
  • Three of five Ca(2+) ligands in the C2B domain were essential for Ca(2+)-dependent translocation.
  • Mutant Doc2β translocation efficiency correlated with enhanced asynchronous neurotransmitter release.
  • Synaptotagmin 1 chimeras with Doc2β loops exhibited slower in vitro kinetics and slower excitatory postsynaptic current decays in neurons.

Conclusions:

  • Specific Ca(2+) binding sites in the Doc2β C2B domain are crucial for its function as a Ca(2+) sensor.
  • Doc2β's role in mediating slow synaptic transmission is determined by these key residues.
  • These findings provide insights into the molecular mechanisms underlying asynchronous neurotransmitter release.