PT - JOURNAL ARTICLE AU - Bhavya Ravi AU - Jian Zhao AU - Sana Chaudhry AU - Mattingly Bartole AU - Richard J. Kopchock, 3rd AU - Christian Guijarro AU - Lijun Kang AU - Kevin M. Collins TI - Presynaptic Gα<sub>o</sub> (GOA-1) signals to depress command neuron excitability and allow stretch-dependent modulation of egg laying in <em>Caenorhabditis elegans</em> AID - 10.1101/701664 DP - 2020 Jan 01 TA - bioRxiv PG - 701664 4099 - http://biorxiv.org/content/early/2020/05/31/701664.short 4100 - http://biorxiv.org/content/early/2020/05/31/701664.full AB - 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 maintains 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.Competing Interest StatementThe authors have declared no competing interest.