Glutamate and acetylcholine corelease at developing synapses.

Wenchang Li, SR Soffe, A Roberts

Research output: Contribution to journalArticlepeer-review

79 Citations (Scopus)

Abstract

Most neurons release a single fast-acting low-molecular-weight transmitter at synapses to activate and open postsynaptic ion channels. We challenge this principle with evidence for corelease of the two major excitatory transmitters, glutamate and acetylcholine (ACh), from single identified neurons in the developing frog tadpole spinal cord. Whole-cell patch electrodes were used to record from single spinal neurons. When action potentials and inhibition were blocked, spontaneous miniature excitatory postsynaptic currents (mEPSCs) were recorded. These were fully blocked only by joint application of glutamate [alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR)] and nicotinic ACh receptor (nAChR) antagonists. Fast nAChR and slow NMDAR mEPSCs were isolated pharmacologically. We then show that some mEPSCs have both the fast nAChR rise and slow NMDAR decay and conclude that some individual synaptic vesicles corelease glutamate and ACh Whole-cell recordings from pairs of neurons were then used to identify the spinal interneurons coreleasing the two excitatory transmitters. One anatomical class of interneuron with descending axons was found to excite other spinal neurons by activating nAChR, AMPAR, and NMDAR simultaneously at its synapses. Although Jonas, Bischofberger, and Sandkuhler [Jonas, P., Bischofberger, J. & Sandkuhler, J. (1998) Science 281, 419-424] showed that the inhibitory transmitters GABA and glycine can be coreleased at spinal synapses, the Xenopus tadpole provides a case where the two main CNS excitatory transmitters are released from single vesicles, and where the presynaptic neuron coreleasing two transmitters has been identified.

Original languageEnglish
Pages (from-to)15488-15493
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number43
DOIs
Publication statusPublished - 26 Oct 2004

Keywords

  • BRAIN-STEM MOTONEURONS
  • VESICULAR GLUTAMATE
  • XENOPUS-LAEVIS
  • SPINAL NEURONS
  • GABA
  • RECEPTORS
  • RELEASE
  • EMBRYOS
  • GLYCINE
  • COTRANSMISSION

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