title: Release-dependent feedback inhibition by a presynaptically localized ligand-gated anion channel.
abstract: Presynaptic ligand-gated ion channels (LGICs) have long been proposed to affect neurotransmitter release and to tune the neural circuit activity. However, the understanding of their in vivo physiological action remains limited, partly due to the complexity in channel types and scarcity of genetic models. Here we report thatC. elegansLGC-46, a member of the Cys-loop acetylcholine (ACh)-gated chloride (ACC) channel family, localizes to presynaptic terminals of cholinergic motor neurons and regulates synaptic vesicle (SV) release kinetics upon evoked release of acetylcholine. Loss oflgc-46prolongs evoked release, without altering spontaneous activity. Conversely, a gain-of-function mutation oflgc-46shortens evoked release to reduce synaptic transmission. This inhibition of presynaptic release requires the anion selectivity of LGC-46, and can ameliorate cholinergic over-excitation in aC. elegansmodel of excitation-inhibition imbalance. These data demonstrate a novel mechanism of presynaptic negative feedback in which an anion-selective LGIC acts as an auto-receptor to inhibit SV release.
authors: Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, San Diego, United States.
authors: Seika
authors: S
authors: Takayanagi-Kiya
authors: Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, San Diego, United States.|Howard Hughes Medical Institute, University of California, San Diego, San Diego, United States.
authors: Keming
authors: K
authors: Zhou
authors: Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, San Diego, United States.|Howard Hughes Medical Institute, University of California, San Diego, San Diego, United States.
authors: Yishi
authors: 0000-0002-9371-9860
authors: Y
authors: Jin
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D018118:Chloride Channels / Q000378:metabolism*; D059329:Cholinergic Neurons / Q000201:enzymology*; D005071:Evoked Potentials; D025461:Feedback, Physiological; D009046:Motor Neurons / Q000201:enzymology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D017729:Presynaptic Terminals / Q000201:enzymology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D018118:Chloride Channels; C000625491:LGC-46 protein, C elegans; D018377:Neurotransmitter Agents
keywords: ACC channels; C. elegans; SV release kinetics; neuroscience; presynaptic autoreceptor