Presynaptic Gαo (GOA-1) signals to depress command neuron excitability and allow stretch-dependent modulation of egg laying in Caenorhabditis elegans

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 G alpha(o), a conserved Pertussis Toxin-sensitive G protein, signals within HSN to inhibit egg-laying circuit activity and prevent entry into the active state. G alpha(o) signaling hyperpolarizes HSN, reducing HSN Ca2+ activity and input onto the postsynaptic vulval muscles. Loss of inhibitory G alpha o 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 G alpha(o)-independent mechanisms in the HSNs and G alpha(o)-dependent mechanisms in cells other than the HSNs. Thus, neuropeptide and inhibitory G alpha(o) 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.

Automated summary

The study demonstrates that G alpha(o) signaling within the HSN inhibits egg-laying circuit activity, preventing entry into the active state. Loss of inhibitory G alpha o signaling causes precocious entry into the egg-laying active state. Feedback mechanisms involving vulval opening and egg release activate neuroendocrine cells.