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Receptors with opposing functions are in postsynaptic microdomains under one presynaptic terminal

Nature Neuroscience volume 3, pages 126–132 (2000)Cite this article

Abstract

Fast excitatory synaptic transmission through vertebrate autonomic ganglia is mediated by postsynaptic nicotinic acetylcholine receptors (nAChRs). We demonstrate a unique postsynaptic receptor microheterogeneity on chick parasympathetic ciliary ganglion neurons—under one presynaptic terminal, nAChRs and glycine receptors formed separate but proximal clusters. Terminals were loaded with [3H]glycine via the glycine transporter-1 (GlyT-1), which localized to the cholinergic presynaptic terminal membrane; depolarization evoked [3H]glycine release that was calcium independent and blocked by the GlyT-1 inhibitor sarcosine. Ganglionic synaptic transmission mediated by nAChRs was attenuated by glycine. Coexistence of separate clusters of receptors with opposing functions under one terminal contradicts Dale's principle and provides a new mechanism for modulating synaptic activity in vivo.

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Figure 1: Ultrastructural localization of nAChRs, GlyRs and gephyrin at discrete postsynaptic membrane microdomains under the calyx-type presynaptic terminal on E15–17 chick ciliary neurons in vivo.
Figure 2: Segregation of nAChR clusters from clusters of GlyRs and their directly associated protein gephyrin in postsynaptic membrane microdomains, including those under separate cholinergic bouton-type terminals on CG choroid neurons.
Figure 3: Inhibitory GlyR response in CG neurons.
Figure 4: Glycine transporter localization and glycine uptake and release in the CG.

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Acknowledgements

We acknowledge Heinrich Betz for providing glycine receptor and gephyrin antibodies and clones, Yimen Ge (Massachusetts General Hospital, Harvard Medical School) for assistance with the laser-scanning confocal microscope and Kathleen Dunlap, Daniel Jay and Tim Turner for advice and comments on the manuscript. This work was supported by NIH grant 21725 to M.H.J.

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  1. The first two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neuroscience, Tufts University School of Medicine, 136 Harrison Ave., Boston, 02111, Massachusetts, USA

    Guoshan Tsen, Brian Williams, Yu-Dong Zhou & Michele H. Jacob

  2. Blackstone-Millville Regional High School, 175 Lincoln St., Blackstone, 01504, Massachusetts, USA

    Pauline Allaire

  3. Dept. of Psychiatry, Wayne State University Med. Ctr. , 540 E. Canfield St., Detroit, 48201, Michigan, USA

    Ognian Ikonomov

  4. Department of Infectious Disease, Tufts University Veterinary School, 200 Westboro Rd., Grafton, 01536, Massachusetts, USA

    Ivanela Kondova

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  1. Guoshan Tsen
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Correspondence to Michele H. Jacob.

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Tsen, G., Williams, B., Allaire, P. et al. Receptors with opposing functions are in postsynaptic microdomains under one presynaptic terminal. Nat Neurosci 3, 126–132 (2000). https://doi.org/10.1038/72066

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