Modulation of feeding by dopamine and serotonin in Drosophila

描述（由申请人提供）：喂养法规对于确保动物消耗与其能量需求成比例的卡路里至关重要。调节进食的神经调节系统失衡可能导致肥胖和饮食失调，并带来严重的健康相关后果。这项提议的长期目标是增加对调节食物摄入的分子信号通路及其相互作用的理解，这对于设计控制肥胖和饮食失调的合理方法至关重要。单胺类神经递质，多巴胺和血清素，相反地调节进食。在哺乳动物中，多巴胺促进进食，而血清素抑制进食。初步研究表明，多巴胺和血清素调节黑腹果蝇的摄食，并确定了促进摄食的多巴胺能神经元和抑制摄食的血清素能神经元。果蝇神经系统的相对简单提供了一个易于处理的模型来解剖多巴胺和血清素如何相反地调节摄食。目的1将研究血清素能神经元的活性是否在响应外部味觉线索和内部生理状态时双向控制摄食行为。Aim 2将测试多巴胺和血清素在短时间尺度上调节进食，以及在长时间尺度上根据内部生理状态调节进食的假设。目的3将研究多巴胺和血清素是否是作用于相同或不同神经元以调节进食的对立信号。提出的分子遗传学，电生理和行为方法将提供在其他系统中难以实现的多巴胺和血清素功能的全面分析。这些研究将提供如何

DESCRIPTION (provided by applicant): Feeding regulation is essential to ensure that animals consume calories in proportion to their energy requirements. An imbalance of neuromodulatory systems that regulate feeding may result in obesity and eating disorders, with significant health-related consequences. The long-term objective of this proposal is to increase understanding of the molecular signaling pathways that regulate food intake and how they interact, crucial for devising rational approaches toward controlling obesity and eating disorders. The monoaminergeric neurotransmitters, dopamine and serotonin, oppositely regulate feeding. In mammals, dopamine promotes feeding and serotonin inhibits it. Preliminary studies of this proposal showed that dopamine and serotonin regulate feeding in the fruit fly Drosophila melanogaster and identified the dopaminergic neurons that promote feeding and serotonergic neurons that inhibit feeding. The relative simplicity of the fruit fly nervous system provides a tractable model to dissect how dopamine and serotonin oppositely regulate feeding. Aim 1 will examine whether the activity of serotonergic neurons bidirectionally controls feeding behavior in response to external gustatory cues and internal physiological state. Aim 2 will test the hypothesis that dopamine and serotonin act over short timescales to regulate feeding during a meal as well as over longer timescales to adjust feeding based on internal physiological state. Aim 3 will examine whether dopamine and serotonin are opponent signals that act on the same or different neurons to modulate feeding. The proposed molecular genetic, electrophysiological and behavioral approaches will provide a comprehensive analysis of dopamine and serotonin function that is difficult to achieve in other systems. These studies will provide insight into how the monoaminergic neurotransmitter systems exercise control over feeding and will significantly advance understanding of feeding modulation, an essential foundation relevant for human health and disease.