Complex behaviors are often composed of discrete, more short-lived behavioral states. However, we have only a limited understanding of the neural mechanisms responsible for establishing the duration of specific behavioral states and for orchestrating transitions between them. Neuropeptides are attractive candidates to orchestrate transitions between states and neuropeptide signaling mechanisms are highly conserved throughout the animal kingdom. We have been using the Caenorhabditis elegans egg-laying circuit as a model to investigate neuropeptidergic control of behavioral transitions. C. elegans egg-laying involves transitions between active and inactive phases, and the relatively simple circuit provides an experimentally tractable model. By analysis of loss-of-function mutants, we found that neuropeptides encoded by the genes
nlp-7 and
flp-11 act redundantly to inhibit transitions from the inactive to the active phase of egg-laying. Thus, our analysis suggests these neuropeptides set the duration of the inactive phase. Reporter gene expression studies revealed that both genes are expressed in cells involved in the control of egg-laying, including the VC4 and VC5 motor neurons and the neurosecretory
uv1 cells, raising the interesting possibility that local secretion of these neuropeptides may provide temporal control over neural activity in the egg-laying circuit. To gain insights into potential NLP-7 mechanism of action, we used cell-specific overexpression of
nlp-7 to demonstrate that expression in the
uv1 cells is both necessary and sufficient to inhibit egg-laying. The inhibitory effects of
nlp-7 overexpression were completely suppressed by combined loss of
egl-47 and
goa-1 function, 2 genes previously implicated in HSN control of egg-laying (Moresco, J.J. & Koelle M.R., 2004, Tanis J.E. et. el., 2008).
nlp-7 overexpression also eliminated egg-laying responses to photostimulation of the HSNs, suggesting either a deficit in serotonin (5-HT) release from the HSNs or reduced responsiveness of vulval muscles to 5-HT. Exogenously supplied 5-HT reversed the inhibitory effects of
nlp-7 overexpression, providing evidence that vulval muscle function is unaffected. Together, our results support a model where neuropeptide secretion from a group of non-neuronal cells (
uv1 cells) regulates the transition between distinct phases of egg-laying by inhibiting neurotransmitter release from egg-laying output neurons.