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

线虫行为状态灵活感觉控制的神经机制

• 批准号: 10659880
• 负责人: Steven Willem Flavell
• 金额: $ 38.21万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10659880
• 关键词: Afferent Neurons; Animal Feed; Animals; Architecture; Behavior; Behavior Control; Behavioral; Brain; Caenorhabditis elegans; Calcium; Cells; Chemoreceptors; Complex; Coupling; Cues; Data; Desire for food; Detection; Environment; Exhibits; Exposure to; Food; Food deprivation (experimental); Generations; Genetic; Image; Imaging Device; Ingestion; Intestines; Link; Locomotion; Logic; Mediating; Metabolic; Molecular; Movement; Nematoda; Nervous System; Neural Pathways; Neuromodulator; Neurons; Neurosciences; Odors; Partner in relationship; Pathway interactions; Physiological; Population; Population Control; Probability; Satiation; Sensory; Sensory Receptors; Signal Transduction; Smell Perception; Source; Speed; Starvation; Synapses; System; Work; behavior influence; behavior prediction; behavior test; behavioral response; experience; feeding; fighting; flexibility; food environment; genome-wide analysis; neural; neural circuit; neuromechanism; olfactory receptor; receptor expression; response; sensory system; stressor; tool

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.

动物的行为状态——无论是活跃、不活跃、交配还是战斗——都会深刻地影响 它如何对环境线索产生行为反应然而，因为环境是。 不断变化的动物经常以感官驱动的方式切换行为状态。 时间尺度、经验和生理变化可能会进一步使动物偏向某些状态。 例如，饥饿的动物可能会表现出更高的概率切换到稳定的居住状态 与吃饱的动物相比，闻到食物的气味后，动物的神经系统如何灵活变化。 产生适合情境的行为状态仍然知之甚少。 线索影响行为状态以及感官线索与行为状态之间的联系如何灵活 变化，检查感觉外围的神经元如何进入关键神经群体至关重要 控制行为状态的生理变化（例如饥饿）可能会影响感觉回路。 本身，以及这些电路与控制行为的下游神经元的相互作用 线虫神经系统对于解决这些类型的全电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) 每个神经元都可以被识别 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 操纵该系统中的单个细胞，线虫在进食时在两种稳定的行为之间切换。 州：居住州，他们减少迁徙以开发食物区；以及漫游州，他们在这些州 它们表现出快速的运动来探索更好的食物来源。 状态受到动物摄入食物、嗅觉线索的检测和饱腹感的影响。 很明显，这些状态受到嗅觉线索和饱腹感、分子途径和神经元的影响。 我们对调节这些效应的电路知之甚少，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 食物感应嗅觉神经元中嗅觉受体表达的广泛变化，进而影响 我们还描述了动物的漫游/居住状态。 现在我们有机会研究如何产生漫游和停留状态。 来自一组定义的化学感应神经元（其感觉受体动态变化）的输入是 由下游电路集成以灵活控制行为状态我们将首先揭示分子和 允许多种外部和内部线索调节嗅觉受体表达的神经通路 定义线虫神经元（目标 1）然后，我们将研究化学感应神经元的集合。 影响饱足状态下漫游-居住回路的活动（目标 2）。 理解感觉外围神经元群体如何灵活控制行为的范例。