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Related Experiment Videos

Glutamate and acetylcholine corelease at developing synapses.

W-C Li1, S R Soffe, Alan Roberts

  • 1School of Biological Sciences, University of Bristol, Woodland Road, Bristol BS8 1UG, United Kingdom. wenchang@li.bristol.ac.uk

Proceedings of the National Academy of Sciences of the United States of America
|October 21, 2004
PubMed
Summary

This study reveals that individual neurons can release both glutamate and acetylcholine (ACh) simultaneously. This challenges the single-transmitter principle and identifies specific spinal interneurons responsible for this dual neurotransmitter corelease in developing frog tadpoles.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Developmental Biology

Background:

  • Neurons traditionally release a single neurotransmitter per synapse.
  • The corelease of multiple transmitters from single vesicles is a less understood phenomenon.
  • Excitatory neurotransmission in the central nervous system (CNS) primarily involves glutamate and acetylcholine.

Purpose of the Study:

  • To investigate the principle of single neurotransmitter release at synapses.
  • To provide evidence for the corelease of glutamate and acetylcholine (ACh) from single neurons.
  • To identify the specific neuronal populations responsible for dual excitatory neurotransmitter corelease.

Main Methods:

  • Whole-cell patch-clamp electrophysiology was used to record from single spinal neurons in developing frog tadpoles.

Related Experiment Videos

  • Pharmacological isolation of miniature excitatory postsynaptic currents (mEPSCs) using specific receptor antagonists.
  • Identification of coreleasing interneurons through paired recordings and anatomical characterization.

    • Main Results:

    • Spontaneous mEPSCs were blocked only by combined glutamate and nicotinic acetylcholine receptor (nAChR) antagonists.
    • Pharmacological isolation revealed distinct fast nAChR and slow N-methyl-D-aspartate receptor (NMDAR) mediated currents.
    • Some mEPSCs exhibited characteristics of both nAChR and NMDAR activation, indicating corelease from single vesicles.
    • A specific class of spinal interneurons with descending axons was identified as coreleasing glutamate and ACh.

    Conclusions:

    • Individual synaptic vesicles can corelease the major excitatory transmitters glutamate and acetylcholine.
    • This finding challenges the long-held principle of single neurotransmitter release per synapse.
    • The identified spinal interneurons simultaneously activate nAChR, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and NMDAR at their synapses.