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

我们每天的选择和决定都反映了我们当前的内在状态。我们的即时行动，以及我们如何记住感官体验，都强烈依赖于我们的内部状态。例如，当我们饿的时候，食物不仅闻起来和尝起来更好，我们对这顿饭的记忆也会增强。先前提出，感觉神经元的神经调节通过过滤感觉经验来促进感觉处理和动物行为中的状态依赖性长期变化。然而，支持这一作用的实验证据以及器官生理学和感觉加工之间的机械联系仍然不足。在这里，我建议使用一个模型系统的基础上，女性生殖状态依赖的行为，我们最近开发的解决两个重要的问题，使用行为分析，光学生理学和遗传学的组合：（1）内部器官如何沟通内部状态，以调节感觉神经元的反应？(2)，感觉神经调节在动物行为的长期变化中发挥了哪些具体作用？包括怀孕在内的生殖状态影响女性对气味和味道的感官知觉。利用模式生物黑腹果蝇，我们最近表明，一个G蛋白偶联受体（GPCR）依赖的特定的气味和味觉感觉神经元的神经调节是必要的，足以改变女性的选择行为交配时，以配合她改变了内部状态。令人惊讶的是，虽然这种感觉神经元的调节只持续了几个小时，但交配后的雌性却能保持这种新的选择行为几天。此外，虽然我们知道感觉神经元中的神经调质及其受体，但连接内脏或神经的初始交配信号及其在感觉神经元中启动神经调节的作用仍然难以捉摸。因此，我们以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，我们将描述来自遗传筛选的候选分子作为来自内部器官和神经的信号的作用，并解开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的假定介质的作用。在第二个工作包中，我们将绘制将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其他神经调节。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的形成，从而通过感觉过滤促进长期行为变化。因此，这两个工作包都涉及普遍感兴趣的问题，并嵌入到我们实验室近年来开发的一个完善的实验框架中。

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.