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Related Concept Videos

Excitatory and Inhibitory Effects of Neurotransmitters01:29

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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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Neuroligin3 splice isoforms shape inhibitory synaptic function in the mouse hippocampus.

Motokazu Uchigashima1,2, Ming Leung3, Takuya Watanabe1

  • 1Brudnick Neuropsychiatric Research Institute, Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

The Journal of Biological Chemistry
|May 9, 2020
PubMed
Summary

Neuroligin 3 (NLGN3) protein isoforms differentially regulate inhibitory synaptic transmission, impacting excitatory-inhibitory balance in the brain. Understanding these neuroligin gene splice variants is key to neurodevelopmental research.

Keywords:
CA1 pyramidal neuronGABA receptorexcitatory and inhibitory balanceglutamate receptorhippocampusneurobiologyneuroligin 3 (NLGN3)neuronneurotransmitter receptorsplice variantssynapsesynaptic transmissiontrans-synaptic cell adhesion

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Synapse formation is crucial for brain development and neuronal circuitry maturation.
  • Proper excitatory-inhibitory (E-I) balance is vital for synaptic activity, and its dysregulation is linked to neurodevelopmental disorders like autism spectrum disorders.
  • The precise molecular mechanisms governing E-I balance require further elucidation.

Purpose of the Study:

  • To investigate the role of neuroligin (Nlgn) genes, specifically Nlgn3, in regulating E-I balance in murine CA1 pyramidal neurons.
  • To explore how Nlgn3 splice isoforms and their subcellular localization influence synaptic function.
  • To identify the major Nlgn genes and their splice isoform expression patterns in the hippocampus.

Main Methods:

  • Single-cell transcriptomics (scRNA-Seq)
  • Immunohistochemistry
  • Electrophysiology
  • Organotypic hippocampal slice cultures from murine models

Main Results:

  • The NLGN3 protein exhibits differential regulation of inhibitory synaptic transmission based on splice isoform.
  • Distinct subcellular localizations of NLGN3 isoforms contribute to functional variations.
  • Nlgn1 and Nlgn3 are identified as the predominant Nlgn genes in mice, with diverse splice isoform expression in CA1 pyramidal neurons.

Conclusions:

  • Results reveal isoform-specific effects of Nlgn genes on E-I balance in the murine hippocampus.
  • This study provides insights into the molecular mechanisms underlying E-I balance and its potential role in neurodevelopmental disorders.