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Glycine-receptor activation is required for receptor clustering in spinal neurons

Nature volume 392, pages 717–720 (1998)Cite this article

Abstract

The ability of nerve cells to receive up to several thousands of synaptic inputs from other neurons provides the anatomical basis for information processing in the vertebrate brain. The formation of functional synapses involves selective clustering of neurotransmitter receptors at presumptive postsynaptic regions of the neuronal plasma membrane1,2,3,4. Receptor-associated proteins are believed to be crucial for this process. In spinal neurons, synaptic targeting of the inhibitory glycine receptor (GlyR)5,6 depends on the expression of the anchoring protein gephyrin7,8,9. Here we show that the competitive GlyR antagonist strychnine and L-type Ca2+-channel blockers inhibit the accumulation of GlyR and gephyrin at postsynaptic membrane areas in cultured rat spinal neurons. Our data are consistent with a model in which GlyR activation that results in Ca2+ influx is required for the clustering of gephyrin and GlyR at developing postsynaptic sites. Similar activity-driven mechanisms may be of general importance in synaptogenesis.

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Figure 1: Effect of strychnine treatment on the distribution of GlyR and gephyrin in spinal cultures.
Figure 2: Dose-response curves showing the effect of strychnine on the synaptic localization and number of cells with intracellular accumulation of GlyR immunoreactivity.
Figure 3: Effects of Ca2+-channel blockers and strychnine analogues on GlyR internalization and synaptic targeting.
Figure 4: A model for activity-dependent GlyR clustering at developing postsynaptic sites.

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Acknowledgements

We thank I. Bartnik for technical assistance and V. O'Connor, R. Harvey and A.Püschel for critically reading the manuscript. This work was supported by grants from the Deutsche Forschungsgemeinschaft and Fonds der Chemischen Industrie. J.K. holds an endowed professorship from the Stifterverband für die Deutsche Wissenschaft.

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  1. Department of Neurochemistry, Max-Planck-Institute for Brain Research, Deutschordenstrasse 46, 60528, Frankfurt/Main, Germany

    J. Kirsch & H. Betz

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Correspondence to J. Kirsch.

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Kirsch, J., Betz, H. Glycine-receptor activation is required for receptor clustering in spinal neurons. Nature 392, 717–720 (1998). https://doi.org/10.1038/33694

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