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Synaptic Components, Function and Modulation Characterized by GCaMP6f Ca2+ Imaging in Mouse Cholinergic Myenteric

Joseph F Margiotta1, Kristen M Smith-Edwards2, Andrea Nestor-Kalinoski3

  • 1Department of Neurosciences, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, United States.

Frontiers in Physiology
|August 19, 2021
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Summary
This summary is machine-generated.

This study reveals how cholinergic neurons in the gut

Keywords:
ionotropic serotonin receptor (5-HT3R)mousemyentericnicotinic acetylcholine receptor (nAChR)synapse

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Area of Science:

  • Neuroscience
  • Gastroenterology
  • Physiology

Background:

  • Intestinal muscle function relies on synaptic circuits in the myenteric plexus.
  • Previous electrophysiology studies disrupt tissue and lack biochemical neuronal detail.
  • Understanding these circuits is crucial for gut motility and function.

Purpose of the Study:

  • To visualize activity in specific gut neurons without tissue disruption.
  • To identify the receptors and synaptic mechanisms controlling cholinergic myenteric ganglion neurons.
  • To explore presynaptic modulation of these neuronal circuits.

Main Methods:

  • Engineered mice to express the Ca2+ indicator GCaMP6f in choline acetyltransferase (ChAT)-expressing neurons.
  • Utilized non-invasive Ca2+ imaging in intact colon segments.
  • Employed receptor agonists, antagonists, and electrical stimulation to probe synaptic function.

Main Results:

  • Cholinergic myenteric ganglion neurons express nicotinic acetylcholine receptors (nAChRs) and serotonin 5-HT3 receptors.
  • Spontaneous and evoked Ca2+ transients in these neurons are mediated by nAChRs and/or 5-HT3Rs via fast synaptic transmission.
  • These synaptic circuits are subject to extensive presynaptic modulation, including by PACAP.

Conclusions:

  • Direct and modulatory synaptic inputs significantly influence cholinergic myenteric ganglion neurons.
  • GCaMP6f/ChAT imaging provides a powerful tool for studying gut neuronal circuits in situ.
  • Findings elucidate the synaptic basis of gut peristalsis and potential targets for motility disorders.