Muscle-directed mechanosensory feedback activates egg-laying circuit activity and behavior in Caenorhabditis elegans.

Mechanosensory feedback of the internal reproductive state drives decisions about when and where to reproduce. For instance, stretch in the Drosophila reproductive tract produced by artificial distention or from accumulated eggs regulates the attraction to acetic acid to ensure optimal oviposition. How such mechanosensory feedback modulates neural circuits to coordinate reproductive behaviors is incompletely understood. We previously identified a stretch-dependent homeostat that regulates egg laying in Caenorhabditis elegans. Sterilized animals lacking eggs show reduced Ca transient activity in the presynaptic HSN command motoneurons that drive egg-laying behavior, while animals forced to accumulate extra eggs show dramatically increased circuit activity that restores egg laying. Interestingly, genetic ablation or electrical silencing of the HSNs delays, but does not abolish, the onset of egg laying, with animals recovering vulval muscle Ca transient activity upon egg accumulation. Using an acute gonad microinjection technique to mimic changes in pressure and stretch resulting from germline activity and egg accumulation, we find that injection rapidly stimulates Ca activity in both neurons and muscles of the egg-laying circuit. Injection-induced vulval muscle Ca activity requires L-type Ca channels but is independent of presynaptic input. Conversely, injection-induced neural activity is disrupted in mutants lacking the vulval muscles, suggesting "bottom-up" feedback from muscles to neurons. Direct mechanical prodding activates the vulval muscles, suggesting that they are the proximal targets of the stretch-dependent stimulus. Our results show that egg-laying behavior in C. elegans is regulated by a stretch-dependent homeostat that scales postsynaptic muscle responses with egg accumulation in the uterus.