Decoding modality-specific circuit function and neuromodulation in the Drosophila nociceptive network

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How specific behaviors are generated by sensory input-specific activation of neuronal networks is of fundamental importance for understanding nervous system function. This is also true for nociception, the ability to perceive and avoid harmful stimuli. Environmental inputs including heat and strong mechanical stimuli, which can be potentially harmful to an organism, are generally perceived as nociceptive and elicit a strong avoidance or escape response. The mammalian and Drosophila nociceptive systems are able to perceive and distinguish different noxious modalities including mechanical stimuli and high temperature. How these noxious cues are encoded by the underlying network and give rise to escape behavior is not fully understood. Using the Drosophila larval nociceptive network, we aim to elucidate the divergent encoding of noxious mechanical and thermal stimuli in this system. In Drosophila larvae, noxious heat or mechanical stimulation gives rise to a similar, highly stereotyped escape response. However, our previous work has shown that the underlying sensory networks differ and differentially require the action of a neuropeptide, the Neuropeptide Y homolog short Neuropeptide F (sNPF), for proper function. Using anatomical, functional and behavioral analyses, we aim to dissect the neuronal network subsets involved in mechano- or thermonociception. We will further investigate the relevant sources of the sNPF peptide, which are required to facilitate behavioral responses to heat or mechanical stimulation. Lastly, we will identify the neuronal subsets responding to sNPF and analyze the downstream signaling responses mediated by its receptor.Altogether, these approaches aim to elucidate how specific noxious stimuli elicit discrete neuronal network responses through recruitment of neuropeptide signaling.