hmc, a cell with previously unknown function couples neuropeptide transmitters with muscle contraction during a rhythmic behavior in C. elegans

Abstract

Abstract Neuropeptides in the brain have both excitatory and inhibitory effects on neuronal activity through paracrine signaling to local circuits. Here, we show that neuropeptides can activate and inhibit calcium responses in a single target cell of previously unknown function, hmc, in C. elegans. We show that hmc controls a discrete muscle contraction during a rhythmic behavior. Live imaging shows that hmc is activated by the neuropeptide like protein FLP-22 in phase with the pacemaker every 50 seconds. FLP-22 is released from a bifunctional motor neuron AVL and activates the frpr-17 G protein-coupled receptor (GPCR), which leads to the activation of a G alpha s-protein kinase A (PKA) signaling pathway in hmc. PKA signaling is not required for hmc activation but instead potentiates hmc activation. hmc activity is inhibited by signaling from the neuropeptide FLP-9, which functions through the GPCR frpr-21 in hmc. Behavioral, calcium imaging, and genetic studies suggest that hmc itself is not contractile but is functionally coupled to muscles through gap junctions composed of UNC-9/innexin. These results indicate that neuropeptides can function as volume neurotransmitters to control the activity state of a target cell and reveal a function for hmc that may be similar to that of endothelial cells.