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，无活动，交配还是战斗）都会深刻影响 它如何产生对环境线索的行为响应。但是，因为环境是 动物不断变化，通常以感官驱动的方式切换行为状态。更长的时间 时间尺度，经验和身体变化可能会使动物偏向某些州。为了 例如，饥饿的动物可能表现出更高的可能性，即在 与喂养动物相比，闻到食物的气味。神经系统如何灵活地改变以使动物 生成背景 - 适当的行为状态仍然对其理解不多。了解感官 提示影响行为状态以及感觉线索与行为状态之间的联系如何灵活 变化，检查如何在感觉周围馈入关键神经元种群中的神经元如何至关重要 控制行为状态。诸如饥饿之类的生理变化可能会影响感觉电路 本身，以及这些圈子与控制行为的下游神经元的相互作用 国家。秀丽隐杆线虫神经系统对于这些类型的全电路问题特别有吸引力 神经科学是因为（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）已知这些神经元之间的突触连接，（d）遗传工具使我们能够 操纵该系统中的单个单元。喂食时，秀丽隐杆线虫在两个稳定的行为之间切换 国家：居住的国家，他们减少了开发食物补丁的运动，并在漫游状态下 他们展示了快速的运动，以探索以获得更好的食物来源。一代漫游和住宅 国家受动物摄入食物的影响，嗅觉提示和饱腹感的影响。虽然是 显然，这些状态受到嗅觉提示和饱腹感的影响，分子途径和中性 介导这些效果的圈子知之甚少。在这里，我们建议建立新的初步数据 这为我们提供了一个独特的机会来发现这些机制。我们发现食物剥夺导致 食物传感嗅觉神经元中嗅觉受体表达的广泛变化，这又影响了 动物的漫游/居住状态。我们还表征了核心的功能架构 产生漫游和居住状态的神经回路。现在，这使我们有机会研究 来自定义的化学感应神经元（动态变化的感觉受体）的输入是 由下游电路集成以灵活地控制行为状态。我们将首先发现分子和 允许多种外部和内部线索调节嗅觉受体表达的神经途径 定义的秀丽隐杆线虫神经元（AIM 1）。然后，我们将研究化学感应神经元的集合 影响跨饱腹部漫游环路的活动（AIM 2）。这项工作将导致新的 了解在感觉外围的神经元种群如何灵活地控制行为的范式。