Dissecting Molecular and Circuit Mechanisms for Inhibition and Delayed Response of ASI Neurons during Nociceptive Stimulus

Summary: The mechanisms by which off-response neurons stay quiescent during stimulation are largely unknown. Here, we dissect underlying molecular and circuit mechanisms for the inhibition of off-response ASI neurons during nociceptive Cu2+ stimulation. ASIs are inhibited in parallel by sensory neurons ASER, ADFs, and ASHs. ASER activates RIC interneurons that release octopamine (OA) to inhibit ASIs through SER-3 and SER-6 receptors. ADFs release 5-HT that acts on the SER-1 receptor to activate RICs and subsequently inhibit ASIs. Furthermore, it is an inherent property of ASIs that only a delayed on response is evoked by Cu2+ stimulation even when all inhibitory neurons are silenced. Ectopic expression of the ion channel OCR-2, which functions synergistically with OSM-9, in the cilia of ASIs can induce an immediate on response of ASIs upon Cu2+ stimulation. Our findings elucidate the molecular and circuit mechanisms regulating fundamental properties of ASIs, including their inhibition and delayed response. : Guo et al. examine a nociceptive circuit in C. elegans and show that inhibitory neurons release octopamine that inhibits ASIs via ser-3 and ser-6 receptors. ASIs show intrinsic delay in response to Cu2+ stimulation even after removal of inhibition, which can be eliminated by ectopic OCR-2 expression. Keywords: off response, ASI, neural circuits, calcium imaging, optogenetics, Caenorhabditis elegan