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.¹ 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.² 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 Ca²⁺ 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.³ Interestingly, genetic ablation or electrical silencing of the HSNs delays, but does not abolish, the onset of egg laying,^3,4,5 with animals recovering vulval muscle Ca²⁺ transient activity upon egg accumulation.⁶ 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 Ca²⁺ activity in both neurons and muscles of the egg-laying circuit. Injection-induced vulval muscle Ca²⁺ activity requires L-type Ca²⁺ 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.