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When an action potential reaches the presynaptic axon terminal, it releases neurotransmitters from the neuron into the synaptic cleft at a chemical synapse. The released neurotransmitter can be excitatory or inhibitory. The critical criteria commonly used to determine whether a molecule is a neurotransmitter at a chemical synapse are the molecule's presence in the presynaptic neuron. Second, its release is in response to strong presynaptic depolarization. And lastly, the presence of...
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Synaptic integration mainly includes the summation of graded potentials. Graded potentials, regardless of their type, cause subtle alterations in membrane voltage, resulting in either depolarization or hyperpolarization. These incremental changes, when combined or summed, can propel the neuron toward its threshold. Consider, for example, a membrane experiencing a +15 mV shift, causing it to depolarize from -70 mV to -55 mV. In this scenario, graded potentials govern the membrane's ability...
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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, 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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Neurons communicate at synapses, or junctions, to excite or inhibit the activity of other neurons or target cells, such as muscles. Synapses may be chemical or electrical.
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Postsynaptic potential (PSP) refers to a change in the electrical potential of a neuron when neurotransmitters released by presynaptic neurons bind to postsynaptic receptors. This potential can either be excitatory, leading to depolarization and ultimately action potential generation, or inhibitory, leading to hyperpolarization and suppression of the postsynaptic neuron.
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Related Experiment Video

Updated: May 9, 2025

Presynaptically Silent Synapses Studied with Light Microscopy
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A toolbox for ablating excitatory and inhibitory synapses.

Aida Bareghamyan1,2, Changfeng Deng3, Sarah Daoudi1

  • 1Department of Biology, Division of Molecular and Computational Biology, University of Southern California, Los Angeles, United States.

Elife
|April 29, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed novel genetic tools to precisely control neural circuit structure by degrading synaptic proteins. These tools enable specific, reversible ablation of excitatory and inhibitory synapses, offering new ways to study brain function.

Keywords:
E3 ligaseablationexcitatoryinhibitorylight-activatedmouseneuroscienceratsynapse

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Optogenetics and chemogenetics allow manipulation of neuronal activity but lack tools for altering neural circuit structure.
  • Existing methods for modifying neural circuits are limited in specificity and reversibility.

Purpose of the Study:

  • To develop genetically encoded tools for targeted degradation of synaptic scaffolding proteins.
  • To create tools for specific and reversible ablation of excitatory and inhibitory synapses.

Main Methods:

  • Designed E3 ligase-dependent protein degradation systems.
  • Developed a constitutive excitatory synapse ablator (PFE3) targeting PSD-95.
  • Created a light-inducible inhibitory synapse ablator (paGFE3) using a photoactivatable complex.
  • Engineered a chemically inducible inhibitory synapse ablator (chGFE3) using a bio-orthogonal dimerizer.

Main Results:

  • PFE3 efficiently ablated excitatory synapses by degrading PSD-95.
  • paGFE3 specifically degraded Gephyrin and ablated inhibitory synapses upon 400 nm light activation.
  • chGFE3 achieved reversible degradation of inhibitory synapses with a chemical inducer.
  • All tools demonstrated specificity and reversibility in ablating synapses.

Conclusions:

  • Introduced three novel genetically encoded tools for precise manipulation of neural circuit structure.
  • These tools enable targeted, reversible functional ablation of synapses.
  • The developed tools offer new possibilities for dissecting neural circuit function.