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In this study, we address why metabotropic and ionotropic cholinergic signaling pathways are used to facilitate motor behaviors. We demonstrate that a G alpha(q)-coupled muscarinic acetylcholine receptor (mAChR) signaling pathway enhances nicotinic acetylcholine receptor (nAChR) signaling to facilitate the insertion of the Caenorhabditis elegans male copulatory spicules into the hermaphrodite during mating. Previous studies showed that ACh (acetylcholine) activates nAChRs on the spicule protractor muscles to induce the attached spicules to extend from the tail. Using the mAChR agonist Oxo M (oxotremorine M), we identified a GAR-3(mAChR)-G alpha(q) pathway that promotes protractor muscle contraction by upregulating nAChR signaling before mating. GAR-3(mAChR) is expressed in the protractor muscles and in the spicule-associated SPC and PCB cholinergic neurons. However, ablation of these neurons or impairing cholinergic transmission reduces drug-induced spicule protraction, suggesting that drug-stimulated neurons directly activate muscle contraction. Behavioral analysis of gar-3 mutants indicates that, in wild-type males, GAR-3(mAChR) expression in the SPC and PCB neurons is required for the male to sustain rhythmic spicule muscle contractions during attempts to breach the vulva. We propose that the GAR-3(mAChR)/G alpha(q) pathway sensitizes the spicule neurons and muscles before and during mating so that the male can respond to hermaphrodite vulva efficiently.

the journal of neuroscience/the journal of neuroscience

Gα<sub>q</sub>-Coupled Muscarinic Acetylcholine Receptors Enhance Nicotinic Acetylcholine Receptor Signaling in<i>Caenorhabditis elegans</i>Mating Behavior

Gαq-Coupled Muscarinic Acetylcholine Receptors Enhance Nicotinic Acetylcholine Receptor Signaling inCaenorhabditis elegansMating Behavior

Gα_q-Coupled Muscarinic Acetylcholine Receptors Enhance Nicotinic Acetylcholine Receptor Signaling inCaenorhabditis elegansMating Behavior