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

Abstract

Mechanosensory feedback of internal state regulates numerous bodily processes including feeding, defecation, and reproduction. However, how mechanosensory feedback signals to modulate neural circuits and coordinate these behaviors is incompletely understood. Here, we use the egg-laying circuit of C. elegans to test our hypothesis that mechanosensory feedback of egg accumulation promotes the active reproductive behavior state. 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. Direct mechanical prodding activates the vulval muscles, suggesting 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.

Natural variation in theCaenorhabditis elegansegg-laying circuit modulates an intergenerational fitness trade-off

“…Many more genes transmitting environmental and physiological signals via sensory processing are known to regulate C. elegans egg laying (Banerjee et al, 2017;Fenk and Bono, 2015;Ringstad and Horvitz, 2008;Schafer, 2006). Moreover, recent research has uncovered an important role of muscle-directed mechanisms regulating egg-laying through sensation of internal stretch mediated by egg accumulation in utero (Collins et al, 2016;Medrano and Collins, 2022;Ravi et al, 2021Ravi et al, , 2018. This stretch-dependent homeostat directly targets vulval muscles and is sufficient to trigger egg laying when synaptic transmission is reduced or defective, for example, in the absence of HSN command neurons (Medrano and Collins, 2022;Ravi et al, 2021Ravi et al, , 2018.…”

“…Moreover, recent research has uncovered an important role of muscle-directed mechanisms regulating egg-laying through sensation of internal stretch mediated by egg accumulation in utero (Collins et al, 2016;Medrano and Collins, 2022;Ravi et al, 2021Ravi et al, , 2018. This stretch-dependent homeostat directly targets vulval muscles and is sufficient to trigger egg laying when synaptic transmission is reduced or defective, for example, in the absence of HSN command neurons (Medrano and Collins, 2022;Ravi et al, 2021Ravi et al, , 2018. The observation of extensive natural variation in C. elegans egg retention indicates that egg-laying behaviour is likely driven by evolutionary changes of muscle-directed signalling components, for example, by altering the degree of vulva muscle sensitivity in response internal stretch signals.…”

“…3G). Therefore, sensitivity to mechanosensory stimuli triggering the first egg-laying event -likely mechanical stretch depending on the number of accumulated eggs in utero (Collins et al, 2016;Medrano and Collins, 2022;Ravi et al, 2021Ravi et al, , 2018) -appears to be variable among strains. In addition, observed strain differences in egg retention are also consistent with more subtle differences in egg-laying behavioural patterns, such as the duration of inactive egg-laying phases (Fig.…”

“…During active egg-laying phases, the neurotransmitter serotonin and neuropeptides signal via the hermaphrodite specific neurons (HSNs) to increase excitability of vulva muscles cells, causing the rapid sequential release of 4 to 6 eggs (Brewer et al, 2019; Collins et al, 2016; Shyn et al, 2003; Waggoner et al, 1998; Zhang et al, 2008). Additional neuromodulatory signals and mechanosensory feedback regulate temporal patterns of egg-laying activity, which are further modulated by physiological and environmental inputs (Aprison et al, 2022; Fernandez et al, 2020; Koelle, 2018; Medrano and Collins, 2022; Ravi et al, 2021; Ringstad and Horvitz, 2008; Schafer, 2005; Trent et al, 1983). Food signals are required for sustained egg-laying activity (Daniels et al, 2000; Dong et al, 2000; Horvitz et al, 1982; Trent, 1982; Waggoner et al, 1998) whereas diverse stressors (e.g.…”

Mechanical force of uterine occupation enables large vesicle extrusion from proteostressed maternal neurons

“…What is the source of the force that promotes exopher production? Elegant work on the egg laying circuit (comprising the somatic gonad, the HSN and VC neurons, and the vulval and uterine muscle) has provided evidence for mechanical signaling within the egg laying circuit that regulates initiation, promotion and termination of egg laying 31,[57][58][59] . Working backward, exopher-promoting force seems unlikely to derive from the vulva or vulval muscle contractions, since when these cells are genetically disrupted in lin-39(RNAi) or in sem-2 mutants, high levels of exophers still are generated.…”