Peptidergic neuromodulation of microcircuits that control chemosensation-induced behaviors

项目总结 神经肽在调节处理嗅觉和味觉信息的神经回路中发挥重要作用。 信息传递。这种调节通常起到调整动物内部状态(例如，唤醒或食物的水平)的作用 状态)对感觉刺激(如信息素或与食物相关的气味)的行为反应。虽然 特定感觉神经元的神经肽能调制已被描述，从分子和细胞 神经肽影响中枢化学感觉回路的机制尚不清楚。长期目标是 通过解构这一生理过程来表征化学感觉回路的神经肽能调制 过程变成明确定义的、与行为相关的分子和神经元事件。重要的是，改变了 人类的化学感觉通常与某些类型的精神障碍有关，并且在 在分子水平上，化学感觉的神经肽能调制是迈向Under-Med的根本第一步。 坚持并改进对这些疾病的治疗。果蝇模型系统提供了一个很好的平台- 这些研究的形式，因为神经肽能系统可以被精确地操纵，并且对 调节化学感觉诱导的行为的特征良好的回路，例如男性的攻击行为， 是可以测量的。最初的实验将集中在神经肽速激肽上，中心假设是 神经肽在局部作用，影响特定的神经元群体，调节化学感觉信息传递。 从王者到男性的争斗行为。三个具体目标，每个都基于初步的成功，是为了：1)魅力-- 描述调节信息素诱导的男性激动性行为的神经肽能回路，2)表征 神经肽和共同释放的神经递质之间的协同作用，以及3)阐明in-in的细胞基础。 三种神经肽(速激肽、神经肽F和FMRFamide)对男性的相互作用 激励性行为(一种化学感觉引导的行为)。在目标1中，表达速激肽受体的神经元 (Takr86C)的形态特征，以及接受来自攻击促进的突触输入的那些 速激肽能神经元将通过光激活的GFP辅助神经元示踪和活体内检测来鉴定。 Cum成像。在目标2中，速激肽与共表达的神经递质乙酰胆碱之间的相互作用 将被描述为。多肽或递质的释放将被独立地阻止在相关细胞中，并影响 关于下游神经元的活动和行为将进行分析。在目标3中，解剖和生理关系- 表达速激肽、神经肽F或FMRFamide的神经元之间的关系将建立起来，主要 为了更好地理解这三种神经肽如何协同影响信息素处理神经元- 拉尔电路。总之，这里提出的研究将揭示基因和细胞机制 神经肽在生理上影响化学感觉回路以调节行为。这些知识将提供 基本了解嗅觉和味觉是如何被集中控制的，以及 这一过程可能导致对环境线索的非适应性反应。

PROJECT SUMMARY Neuropeptides play important roles in modulating neural circuits that process olfactory and gustatory infor- mation. This modulation generally functions to align an animal's internal state (e.g., levels of arousal, or food status) with behavioral responses to sensory stimuli (e.g., pheromones or food-associated odorants). Although the neuropeptidergic modulation of specific sensory neurons has been described, the molecular and cellular mechanisms by which neuropeptides affect central chemosensory circuits are unknown. The long-term goal is to characterize the neuropeptidergic modulation of chemosensory circuits by deconstructing this physiological process into clearly defined, behaviorally relevant molecular and neuronal events. Importantly, altered chemosensation in humans is often associated with certain types of mental disorders, and characterizing at a molecular level the neuropeptidergic modulation of chemosensation is a fundamental first step toward under- standing and improving treatments for these disorders. The Drosophila model system offers an excellent plat- form for these studies, because neuropeptidergic systems can be precisely manipulated and the effects on well-characterized circuits mediating chemosensation-induced behaviors, such as male aggressive behavior, can be measured. Initial experiments will focus on the neuropeptide tachykinin, with the central hypothesis that neuropeptides act locally to affect a specific population of neurons to modulate chemosensory information rele- vant to male agonistic behavior. The three specific aims, each based on preliminary success, are to: 1) charac- terize the neuropeptidergic circuit that modulates pheromone-induced male agonistic behavior, 2) characterize synergies between neuropeptides and co-released neurotransmitters, and 3) elucidate the cellular basis of in- teractions among three neuropeptide (tachykinin, neuropeptide F and FMRFamide) that each modulate male agonistic behavior (a chemosensation-guided behavior). In Aim 1, neurons expressing the tachykinin receptor (Takr86C) will be morphologically characterized, and those receiving synaptic input from aggression-promoting tachykininergic neurons will be identified via photo-activatable GFP-assisted neuronal tracing and in vivo cal- cium imaging. In Aim 2, interactions between tachykinin and the co-expressed neurotransmitter acetylcholine will be characterized. Peptide or transmitter release will be independently blocked in relevant cells, and effects on downstream neuronal activity and behavior will be analyzed. In Aim 3, anatomical and physiological rela- tionships between neurons expressing tachykinin, neuropeptide F, or FMRFamide will be established, leading to a better understanding of how these three neuropeptides synergistically affect a pheromone-processing neu- ral circuit. Together, the research proposed here will uncover the genetic and cellular mechanisms by which neuropeptides physiologically affect chemosensory circuits to modulate behavior. Such knowledge will provide a fundamental understanding of how smell and taste perception is centrally controlled, and how dysfunction of this process may lead to non-adaptive responses to environmental cues.