Neurogenetic mechanisms of sensory circuit plasticity

项目总结 遗传程序构建引导先天行为的神经电路；它们还实现 赋予这些电路功能fl灵活性。确定这些计划的工作方式对于提供 理解人类神经回路的典型和病理状态的概念性框架。然而， 即使在简单的神经系统中，这些机制也没有被很好地理解。性别差异提供了独特的 了解模型系统中fl可暴露的固有行为的入口点。此外，它们还可以帮助 阐明在人类神经精神疾病中导致性别偏见的机制，如自闭症谱系 精神障碍和焦虑症。在这里，我们提出了利用线虫C. 以提高我们对指定先天行为的遗传机制的理解，并提供 它们具有依赖于状态的可塑性。在最近的工作中，我们发现一对线虫 被称为ADF的化学感觉神经元在决定行为反应的效价方面起着关键作用 蛔虫苷类的性信息素。特别是，adf神经元的性状态是确定fi的充分条件。 无论生物性别，个体是否会被信息素混合物吸引或排斥 身体的其他部分。在这项工作中，我们将利用这一系统提供的独特机会 为了(1)了解遗传性别如何在共享神经回路中实现功能差异，(2)确定 fl中一个保守的神经调节通路(PDF信号)通过其不同的方式利用信息素- 调节两性的行为，以及(3)决定fl中食物的可获得性如何影响回路功能，以提供 对信息素的行为反应是允许的状态。我们的结果很可能预示着fi 增进对遗传程序塑造神经生理学的基本原理的理解 电路，并指定它们生成fl可执行的固有行为的能力。

PROJECT SUMMARY Genetic programs build neural circuits that guide innate behaviors; they also implement mechanisms that endow these circuits with functional flexibility. Determining how these programs work is essential for providing a conceptual framework for understanding typical and pathological states of human neural circuits. However, even in simple nervous systems, these mechanisms are not well understood. Sex differences provide a unique entry point for understanding flexible innate behaviors in model systems. Additionally, they could also help illuminate mechanisms that bring about sex bias in human neuropsychiatric conditions like autism spectrum disorder and anxiety disorders. Here, we propose studies using the exceptional tractability of the nematode C. elegans to advance our understanding of the genetic mechanisms that specify innate behaviors and provide them with state-dependent plasticity. In recent work, we have found that a single pair of C. elegans chemosensory neurons called ADF plays a key role in determining the valence of the behavioral response to ascaroside-class sex pheromones. In particular, the sexual state of the ADF neurons is sufficient to determine whether an individual will be attracted to or repelled by a pheromone mixture, regardless of the biological sex of the rest of the body. In this work, we will take advantage of the unique opportunities provided by this system to (1) understand how genetic sex implements functional differences in shared neural circuitry, (2) identify the means by which a conserved neuromodulatory pathway (PDF signaling) differentially influences pheromone- mediated behavior in both sexes, and (3) determine how food availability influences circuit function to provide a state that is permissive for the behavioral response to pheromones. Our results are likely to significantly advance the understanding of basic principles by which genetic programs sculpt the physiology of neural circuits and specify their ability to generate flexible innate behaviors.