Modulation of feeding by dopamine and serotonin in Drosophila

多巴胺和血清素对果蝇摄食的调节

• 批准号: 8840943
• 负责人: Kristin E Scott
• 金额: $ 32.3万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-25 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8840943
• 关键词: Acute; Animal Feed; Animals; Basic Science; Behavior; Behavioral; Behavioral Mechanisms; Calories; Chronic; Cues; Disease; Dopamine; Dopamine Receptor; Drosophila genus; Drosophila melanogaster; Eating; Eating Disorders; Ensure; Equilibrium; Exercise; Experimental Models; Feeding behaviors; Foundations; Health; Human; Hunger; Lead; Long-Term Effects; Mammals; Mediating; Modeling; Molecular; Molecular Genetics; Nervous system structure; Neurons; Neurotransmitters; Obesity; Pattern; Physiological; Regulation; Relative (related person); Research; Role; Satiation; Serotonin; Signal Pathway; Signal Transduction; Site; System; Testing; Work; base; behavioral study; dopaminergic neuron; feeding; fly; genetic approach; insight; neural circuit; neuroregulation; pleiotropism; response; serotonin receptor

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.

描述（由申请人提供）：饲养法规对于确保动物消耗的卡路里与其能量需求成比例至关重要。调节进食的神经调节系统的失衡可能导致肥胖和饮食失调，并产生严重的健康相关后果。该提案的长期目标是增加对调节食物摄入的分子信号通路以及它们如何相互作用的理解，这对于设计控制肥胖和饮食失调的合理方法至关重要。单胺能神经递质多巴胺和5-羟色胺则相反地调节进食。在哺乳动物中，多巴胺促进摄食，而血清素抑制摄食。这一提议的初步研究表明，多巴胺和血清素调节果蝇的摄食，并确定了促进摄食的多巴胺能神经元和抑制摄食的多巴胺能神经元。果蝇的神经系统相对简单，这提供了一个易于处理的模型来剖析多巴胺和5-羟色胺如何反向调节进食。目的1研究摄食行为是否受味觉信号和生理状态的双向调控。目标2将测试多巴胺和5-羟色胺在短时间尺度上调节进食以及在较长时间尺度上基于内部生理状态调节进食的假设。目标3将研究多巴胺和5-羟色胺是否是作用于相同或不同神经元以调节进食的对立信号。所提出的分子遗传学、电生理学和行为学方法将提供在其他系统中难以实现的多巴胺和5-羟色胺功能的全面分析。这些研究将提供洞察如何 单胺能神经递质系统对摄食进行控制，并将显著地促进对摄食调节的理解，摄食调节是与人类健康和疾病相关的重要基础。