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Presynaptic glycine receptors enhance transmitter release at a mammalian central synapse

Nature volume 411, pages 587–590 (2001)Cite this article

Abstract

Glycine and GABAA (γ-aminobutyric acid A) receptors are inhibitory neurotransmitter-gated Cl- channels localized in postsynaptic membranes. In some cases, GABAA receptors are also found presynaptically, but they retain their inhibitory effect as their activation reduces excitatory transmitter release1,2,3,4. Here we report evidence for presynaptic ionotropic glycine receptors, using pre- and postsynaptic recordings of a calyceal synapse in the medial nucleus of the trapezoid body (MNTB). Unlike the classical action of glycine, presynaptic glycine receptors triggered a weakly depolarizing Cl- current in the nerve terminal. The depolarization enhanced transmitter release by activating Ca2+ channels and increasing resting intraterminal Ca2+ concentrations. Repetitive activation of glycinergic synapses on MNTB neurons also enhanced glutamatergic synaptic currents, indicating that presynaptic glycine receptors are activated by glycine spillover. These results reveal a novel site of action of the transmitter glycine, and indicate that under certain conditions presynaptic Cl- channels may increase transmitter release.

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Figure 1: Enhancement of EPSCs by glycine.
Figure 2: Presynaptic locus of glycine action.
Figure 3: Glycine activates a presynaptic depolarizing Cl- current.
Figure 4: Glycine enhances release by depolarizing the nerve terminal.
Figure 5: Spillover to presynaptic glycine receptors.

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Acknowledgements

We thank S. Brenowitz, H. von Gersdorff and C. Jahr for comments on the manuscript. Supported by NIH grants and a Fogarty International Center Fellowship.

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  1. Oregon Hearing Research Center and Vollum Institute, L-335A, 3181 SW Sam Jackson Park Rd., Portland, 97201, Oregon, USA

    Rostislav Turecek & Laurence O. Trussell

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  1. Rostislav Turecek
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Correspondence to Laurence O. Trussell.

Supplementary information

Figure 1.

Pre- and postsynaptic glycine-evoked currents are independent (GIF 13.1 KB)

Upper panels show postsynaptic glycine-evoked currents, with holding potentials indicated on the left. Lowest panel shows currents recorded simultaneously in the presynaptic terminal, with holding potentials indicated on the left. Glycine (1 mM) was applied during the period marked by the black bar at the top of the Figure. The experiment illustrates that the amplitude and time course of the presynaptic glycine response was independent of the amplitude and direction of chloride current flow in the postsynaptic cell. Thus, the presynaptic response is most likely due to glycine receptors in the presynaptic terminal.

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Turecek, R., Trussell, L. Presynaptic glycine receptors enhance transmitter release at a mammalian central synapse. Nature 411, 587–590 (2001). https://doi.org/10.1038/35079084

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