P_2021_J.Biol.Chem__101466

Complex biological functions within organisms are frequently orchestrated by systemic communication between tissues. In the model organism C. elegans, the pharyngeal and body wall neuromuscular junctions are two discrete structures that control feeding and locomotion, respectively. Separate, well-defined neuromuscular circuits control these distinct tissues. Nonetheless, the emergent behaviours, feeding and locomotion, are coordinated to guarantee the efficiency of food intake. Here we show that pharmacological hyperactivation of cholinergic transmission at the body wall muscle reduces the rate of pumping behaviour. This was evidenced by a systematic screening of the effect of the cholinesterase inhibitor aldicarb on the rate of pharyngeal pumping on food in mutant worms. The screening revealed that key determinants of the inhibitory effect of aldicarb on pharyngeal pumping are located at the body wall neuromuscular junction. In fact, the selective stimulation of the body wall muscle receptors with the agonist levamisole inhibited pumping in a lev-1-dependent fashion. Interestingly, this response was independent of unc-38, an alpha subunit of the nicotinic receptor classically expressed with lev-1 at the body wall muscle. This implies an uncharacterized lev-1-containing receptor underpins this effect. Overall, our results reveal that body wall cholinergic transmission not only controls locomotion but simultaneously inhibits feeding behaviour.