Neural Mechanisms that Underlie Flexible Sensory Control of Behavioral States in C. elegans

动物的行为状态--无论是活跃的、不活跃的、交配的还是争斗的--都会深刻地影响 它如何对环境线索产生行为反应。然而，由于环境 动物经常以感官驱动的方式切换行为状态。在较长 时间尺度、经验和生理变化可能进一步使动物偏向某些状态。为 例如，饥饿的动物可以表现出更高的切换到稳定的停留状态的概率， 闻食物的气味，与喂养的动物相比。神经系统如何灵活地变化， 生成上下文适当的行为状态仍然知之甚少。为了了解感官 线索影响行为状态，以及感觉线索和行为状态之间的联系如何灵活地 改变，这将是至关重要的，以研究如何神经元在感觉周边饲料到关键的神经群体 控制着行为状态饥饿等生理变化可能会影响感觉回路 以及这些回路与控制行为的下游神经元的相互作用 states.梭elegans神经系统对这些类型的全回路问题特别有吸引力， 神经科学，因为（a）它由302个神经元组成，（B）每个神经元都可以在每个神经元中识别。 动物，（c）这些神经元之间的突触连接是已知的，（d）遗传工具使我们能够 操纵这个系统中的单个细胞。取食时，C.在两种稳定的行为模式之间切换 国家：居住国，在那里他们减少了他们的运动，以利用食物补丁，和漫游国， 它们表现出快速的运动来探索更好的食物来源。漫游与栖居的生成 状态受动物对食物的摄取、嗅觉线索的检测和饱腹感的影响。虽然 很明显，这些状态受到嗅觉线索和饱腹感的影响，分子途径和神经系统 对介导这些效应的电路知之甚少。在这里，我们建议建立新的初步数据， 这给了我们一个独特的机会来揭示这些机制。我们发现食物匮乏会导致 在食物敏感嗅觉神经元中嗅觉受体表达的广泛变化，这反过来又影响了嗅觉神经元的功能。 动物的漫游/居住状态。我们还描述了核心的功能架构 产生漫游和居住状态的神经回路。这给了我们一个机会来研究 来自一组确定的化学感觉神经元（其感觉受体动态变化）的输入是 由下游电路集成以灵活地控制行为状态。我们将首先揭示分子和 神经通路，允许不同的外部和内部线索，以调节嗅觉受体的表达， 定义C。elegans神经元（Aim 1）。然后，我们将研究化学感觉神经元的集合 影响饱腹感状态下漫游-居住回路的活动（目标2）。这项工作将导致一个新的 这是理解感觉外周神经元群体如何灵活控制行为的范例。

The behavioral state of an animal – whether it is active, inactive, mating, or fighting – profoundly influences how it generates behavioral responses to environmental cues. However, because the environment is constantly changing, animals often switch behavioral states in a sensory-driven manner. Over longer timescales, experience and physiological changes may further bias animals towards certain states. For example, a starved animal may exhibit a higher probability of switching to a stable dwell ing state upon smelling a food odor, compared to a fed animal. How the nervous system flexibly changes so that animals generate context-appropriate behavioral states remains poorly understood. To understand how sensory cues influence behavioral states and how the links between sensory cues and behavioral states can flexibly change, it will be critical to examine how neurons at the sensory periphery feed into key neural populations that control behavioral states. Physiological changes like starvation may influence sensory circuits themselves, as well as the interactions of these circuits with downstream neurons that control behavioral states. The C. elegans nervous system is particularly attractive for these types of whole-circuit problems in neuroscience because (a) it consists of exactly 302 neurons, (b) every neuron can be identified in every animal, (c) the synaptic connections between these neurons are known, and (d) genetic tools allow us to manipulate single cells in this system. While feeding, C. elegans switch between two stable behavioral states: dwelling states, where they reduce their movement to exploit a food patch, and roaming states, where they display fast locomotion to explore for a better food source. The generation of roaming and dwelling states is influenced by the animal’s ingestion of food, detection of olfactory cues, and satiety. Although it is clear that these states are influenced by olfactory cues and satiety, the molecular pathways and neural circuits that mediate these effects are poorly understood. Here, we propose to build off new preliminary data that gives us a unique opportunity to uncover these mechanisms. We found that food deprivation leads to a broad change in olfactory receptor expression in food-sensing olfactory neurons, which in turn impacts the roaming/dwelling state of the animal. We have also characterized the functional architecture of the core neural circuit that generates roaming and dwelling states. This now gives us an opportunity to examine how inputs from a defined set of chemosensory neurons (whose sensory receptors dynamically change) are integrated by downstream circuits to flexibly control behavioral states. We will first uncover molecular and neural pathways that allow diverse external and internal cues to modulate olfactory receptor expression in defined C. elegans neurons (Aim 1). Then, we will examine how ensembles of chemosensory neurons influence activity in the roaming-dwelling circuit across satiety states (Aim 2). This work will result in a new paradigm for understanding how populations of neurons at the sensory periphery flexibly control behavior.