Neural circuit and molecular mechanisms underpinning mating state-dependent choice behavior in Drosophila females

支持果蝇雌性交配状态依赖选择行为的神经回路和分子机制

• 批准号: 332825742
• 负责人: Professorin Dr. Ilona Grunwald Kadow
• 金额: --
• 依托单位: Institut für Physiologie II
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/332825742?language=en
• 关键词: Neural; circuit; molecular; mechanisms; underpinning

Every day our choices and decisions reflect our current internal state. Our immediate actions, but also how we remember a sensory experience strongly depends on our internal state. For instance, food not only smells and tastes better when we are hungry, our memory of such as meal is enhanced. It was previously proposed that neuromodulation of sensory neurons facilitates sensory processing and state-dependent long-term changes in animal behavior, by filtering sensory experiences. However, experimental evidence supporting this role and the mechanistic connection between organismic physiology and sensory processing remains insufficient. Here, I propose to use a model system based on female reproductive state-dependent behavior that we have recently developed to address two important questions using a combination of behavioral analysis, optical physiology, and genetics: (1) How do internal organs communicate internal states to modulate sensory neuron responses? (2), which concrete role does sensory neuromodulation play in long-term changes of animal behavior?Reproductive states including pregnancy influence a female s sensory perception of odors and tastes. Using the model organism Drosophila melanogaster, we recently showed that a G-protein coupled receptor (GPCR)-dependent neuromodulation of specific odor and taste sensory neurons was necessary and sufficient to change a female s choice behavior upon mating to match her changed internal state. Surprisingly, while this sensory neuron modulation lasted only for a few hours, mated females maintained the new choice behavior for several days. Furthermore, while we know the neuromodulator and its receptor in sensory neurons, the initial mating signal connecting internal organs or nerves and its role in initiating neuromodulation in sensory neurons remained elusive. Therefore, our previous work provides a great framework to address the above posed questions. In a first work package, we will characterize the role of candidate molecules from a genetic screen as signals from internal organs and nerves and unravel the underpinning molecular and neural circuit mechanisms. Furthermore, we will analyze the role of taste receptor neurons in the female gut as putative mediators of internal state and physiology. In a second work package, we will map the neural circuit that connects the identified odor and taste neurons to higher brain centers and address additional neuromodulation in higher neurons. Finally, we will test whether transient modulation of sensory neurons might facilitate memory formation and thereby long-term behavioral changes by sensory filtering. Both work packages therefore deal with questions of general interest and are embedded in a well-established experimental framework that our lab has developed in the recent years.

我们每天的选择和决定都反映了我们当前的内部状态。我们的立即行动以及我们如何记住感官体验在很大程度上取决于我们的内部状态。例如，当我们饥饿时，食物不仅闻起来和尝起来更好，而且我们对食物的记忆也会增强。之前有人提出，感觉神经元的神经调节通过过滤感觉体验来促进动物行为的感觉处理和状态依赖性长期变化。然而，支持这一作用以及有机体生理学和感觉处理之间的机制联系的实验证据仍然不足。在这里，我建议使用我们最近开发的基于女性生殖状态依赖行为的模型系统，结合行为分析、光学生理学和遗传学来解决两个重要问题：（1）内脏器官如何传达内部状态来调节感觉神经元反应？ (2)、感觉神经调节在动物行为的长期变化中发挥哪些具体作用？包括怀孕在内的生殖状态影响雌性对气味和味道的感官知觉。使用模型生物黑腹果蝇，我们最近表明，特定气味和味觉感觉神经元的 G 蛋白偶联受体 (GPCR) 依赖性神经调节对于改变雌性在交配时的选择行为以匹配其改变的内部状态是必要且充分的。令人惊讶的是，虽然这种感觉神经元调节只持续了几个小时，但交配的雌性却将新的选择行为保持了几天。此外，虽然我们知道感觉神经元中的神经调节剂及其受体，但连接内脏或神经的初始交配信号及其在启动感觉神经元中的神经调节中的作用仍然难以捉摸。因此，我们之前的工作为解决上述问题提供了一个很好的框架。在第一个工作包中，我们将把遗传筛选中的候选分子的作用描述为来自内脏和神经的信号，并揭示基础分子和神经回路机制。此外，我们将分析女性肠道中味觉受体神经元作为内部状态和生理学推定调节者的作用。在第二个工作包中，我们将绘制将已识别的气味和味觉神经元连接到高级大脑中心的神经回路，并解决高级神经元中的额外神经调节问题。最后，我们将测试感觉神经元的瞬时调节是否可能促进记忆形成，从而通过感觉过滤促进长期行为变化。因此，这两个工作包都处理普遍感兴趣的问题，并嵌入到我们实验室近年来开发的完善的实验框架中。