A Novel and Functionally Diverse Class of Acetylcholine-Gated Ion Channels.

Hardege I, Morud J, Courtney A, Schafer WR

J. Neurosci. 43 (7) 1111-1124 [2023-02-15; online 2023-01-05]

Fast cholinergic neurotransmission is mediated by acetylcholine-gated ion channels; in particular, excitatory nicotinic acetylcholine receptors play well established roles in virtually all nervous systems. Acetylcholine-gated inhibitory channels have also been identified in some invertebrate phyla, yet their roles in the nervous system are less well understood. We report the existence of multiple new inhibitory ion channels with diverse ligand activation properties in Caenorhabditis elegans We identify three channels, LGC-40, LGC-57, and LGC-58, whose primary ligand is choline rather than acetylcholine, as well as the first evidence of a truly polymodal channel, LGC-39, which is activated by both cholinergic and aminergic ligands. Using our new ligand-receptor pairs we uncover the surprising extent to which single neurons in the hermaphrodite nervous system express both excitatory and inhibitory channels, not only for acetylcholine but also for the other major neurotransmitters. The results presented in this study offer new insight into the potential evolutionary benefit of a vast and diverse repertoire of ligand-gated ion channels to generate complexity in an anatomically compact nervous system.SIGNIFICANCE STATEMENT Here we describe the diversity of cholinergic signaling in the nematode Caenorhabditis elegans We identify and characterize a novel family of ligand-gated ion channels and show that they are preferentially gated by choline rather than acetylcholine and expressed broadly in the nervous system. Interestingly, we also identify one channel gated by chemically diverse ligands including acetylcholine and aminergic ligands. By using our new knowledge of these ligand-gated ion channels, we built a model to predict the synaptic polarity in the C. elegans connectome. This model can be used for generating hypotheses on neural circuit function.

Integrated Microscopy Technologies Gothenburg [Service]

PubMed 36604172

DOI 10.1523/JNEUROSCI.1516-22.2022

Crossref 10.1523/JNEUROSCI.1516-22.2022

pmc: PMC9962794
pii: JNEUROSCI.1516-22.2022

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