Dissection of neural circuitry underlying nociception in Drosophila larvae

DESCRIPTION (provided by applicant): The ability to rapidly withdraw from potentially harmful stimuli is critical for survival. The sensory neurons detecting noxious stimuli have been well characterized, but the interneurons that modify and integrate these signals in the spinal cord remains largely unknown. This is particularly relevant for cases of chronic pain, where aberrant sensitization of interneurons in the spinal cord can elicit a sensation of pain in the absence of noxious stimuli. Studying the neural circuitry underlying nociception is feasible using a simple model, such as Drosophila larvae, which display robust and well-characterized nociceptive behaviors and possess a sophisticated genetic tool kit that allows for cell-specific labeling and manipulation. I have identified a population of interneurons (sLN1s), directly downstream of the primary nociceptive sensory neurons that are required for generating specific nociceptive behaviors. However, silencing sLN1s does not abolish nociceptive behavior, indicating that there are additional interneurons with distinct roles in nociception. This proposal aims (i) to resolve the functional role of these sLN1 interneurons in generating specific nociceptive behaviors; (ii) reconstruct the nociceptive circuit downstream of sLN1s using previously generated serial section electron micrographs and (iii) assess how this assembly of interneurons generates discrete nociceptive behaviors. This research will reveal how noxious information is transformed to behavior, and potentially elucidate the cellular basis for anomalies in the processing of information by nociceptive pathways, including chronic pain states.