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 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. Interestingly, genetic ablation or electrical silencing of the HSNs delays, but does not abolish, the onset of egg laying, with animals recovering vulval muscle Ca2+ 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 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.
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Presynaptic Gαo (GOA-1) signals to depress command neuron excitability and allow stretch-dependent modulation of egg laying in Caenorhabditis elegans
Abstract Egg laying in the nematode worm Caenorhabditis elegans is a two-state behavior modulated by internal and external sensory input. We have previously shown that homeostatic feedback of embryo accumulation in the uterus regulates bursting activity of the serotonergic HSN command neurons that sustains the egg-laying active state. How sensory feedback of egg release signals to terminate the egg-laying active state is less understood. We find that Gαo, a conserved Pertussis Toxin-sensitive G protein, signals within HSN to inhibit egg-laying circuit activity and prevent entry into the active state. Gαo signaling hyperpolarizes HSN, reducing HSN Ca2+ activity and input onto the postsynaptic vulval muscles. Loss of inhibitory Gαo signaling uncouples presynaptic HSN activity from a postsynaptic, stretch-dependent homeostat, causing precocious entry into the egg-laying active state when only a few eggs are present in the uterus. Feedback of vulval opening and egg release activates the uv1 neuroendocrine cells which release NLP-7 neuropeptides which signal to inhibit egg laying through Gαo-independent mechanisms in the HSNs and Gαo-dependent mechanisms in cells other than the HSNs. Thus, neuropeptide and inhibitory Gαo signaling maintain a bi-stable state of electrical excitability that dynamically controls circuit activity in response to both external and internal sensory input to drive a two-state behavior output.
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- Award ID(s):
- 1844657
- NSF-PAR ID:
- 10312835
- Editor(s):
- Bülow, H
- Date Published:
- Journal Name:
- Genetics
- Volume:
- 218
- Issue:
- 4
- ISSN:
- 1943-2631
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/genetics/iyab080
