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

神经网络的感觉输入特异性激活是如何产生特定行为的，这对于了解神经系统的功能是至关重要的。伤害感也是如此，痛觉是感知和避免有害刺激的能力。环境输入，包括热和强烈的机械刺激，可能对生物体造成潜在的伤害，通常被认为是伤害性的，并引起强烈的回避或逃逸反应。哺乳动物和果蝇的伤害性感受系统能够感知和区分不同的伤害方式，包括机械刺激和高温。这些有害的线索是如何被底层网络编码并引发逃避行为的，目前还不完全清楚。利用果蝇幼虫伤害性感受网络，我们旨在阐明该系统中机械和热伤害刺激的不同编码方式。在果蝇幼虫中，有害的高温或机械刺激会引起类似的、高度刻板的逃逸反应。然而，我们以前的工作已经表明，潜在的感觉网络不同，并且不同地需要一种神经肽，神经肽Y同系物短神经肽F(SNPF)的作用，才能发挥正常的功能。利用解剖学、功能学和行为学的分析，我们的目标是剖析涉及机械或热伤害性感觉的神经网络亚群。我们将进一步调查sNPF肽的相关来源，它是促进对热或机械刺激的行为反应所必需的。最后，我们将确定sNPF反应的神经元亚群，并分析其受体介导的下游信号反应。这些方法旨在阐明特定的伤害性刺激如何通过神经肽信号的募集来引发离散的神经元网络反应。

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.