Identifying, manipulating, and studying a complete sensory-to-motor model behavior circuit

识别、操作和研究完整的感觉到运动模型行为回路

• 批准号: 10224770
• 负责人: LISA STOWERS
• 金额: $ 66.56万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224770
• 关键词: Adolescent; Adult; Age; Amygdaloid structure; Anatomy; Behavior; Behavioral; Brain; Brain region; Bypass; Cell Nucleus; Code; Complex; Cues; Data; Deposition; Elements; Elephants; Esthesia; Female; Fiber; Food; Fright; Goals; Hypothalamic structure; Image; Ingestion; Investigation; Knowledge; Learning; Limbic System; Logic; Mediating; Memory; Modeling; Motor; Motor output; Mus; Muscle; Nature; Neurons; Nose; Olfactory Pathways; Output; Pattern; Photometry; Population; Public Health; Reproducibility; Research; Rest; Scientist; Sensory; Skeleton; Smell Perception; Snakes; Social Behavior; Sphincter; Spiders; Stress; Structure; Testing; Texture; Touch sensation; Urethral sphincter; Urine; Viral; Work; awake; base; blind; experience; insight; knowledge of results; male; men; motivated behavior; neural circuit; neuromechanism; olfactory stimulus; optogenetics; programs; relating to nervous system; response; sensory input; sensory stimulus; sensory system; stem; theories; tool

Project Summary How does the brain transform sensory information into complex behavior? The objective of this proposal is to identify the relevant neurons across the brain that are necessary to produce a relatively simple motivated behavior to study and identify fundamental principles underlying coding. Sensory-to-behavior circuits must contain a variety of neural computations such as those that determine the identity and meaning of the sensed cues, gauge internal state, remember previous experience, and command muscle action. However, without knowing all of the parts of a model circuit, studying where and how these computations occur has proven difficult. Currently, complete circuit structure underlying most behaviors is largely unknown, and no complete model circuit has been traversed through the mouse limbic system. Therefore, study of neural coding relies on investigation of single brain regions, such as subdivisions of the amygdala or hypothalamus. Such focus may be akin to blind men touching different parts of an elephant; without perceiving the entirety, interpretation may become distorted. Here we propose that sensation-to-motivated-behavior employs an entire circuit and its study as a whole will accelerate understanding. We will overcome this bottleneck by leveraging the systematic control of the mouse’s olfactory system to elicit urine-marking behavior as an ideal model circuit. Upon smelling females, male mice are motivated to intentionally deposit copious urine marks to advertise their sexual availability. To investigate how this motivated circuit encodes behavior, we will 1) identify a complete, sensory-to-muscle, anatomic circuit that generates behavior, 2) determine the activity patterns of the relevant neurons in relationship to the behavior and to each other, and 3) determine the neural logic across the circuit that integrates internal state and experience. Completion of these aims will provide a unified picture of how a simple motivated behavior is coded in the brain. We expect that it will also provide the experimental means to identify and assign order and structure of basic known and unexpected principles that underlie how information is represented, altered, and integrated as it journeys from initial olfactory sensation to ultimate muscle activity. Once completed, both the approach and resulting knowledge will provide solutions for us and others to use as a template for the mechanistic study of the logic of sensory-to-behavior across other more complex motivated circuits. We anticipate that full knowledge of the parts and activity patterns the complete circuit will provide a crucial first step to understanding of how sensory systems, the brain, and the body collectively generate behavior.

项目概要 大脑如何将感官信息转化为复杂的行为？此举的目的 提议是识别整个大脑中产生神经元所必需的相关神经元。 相对简单的动机行为来研究和识别背后的基本原理 编码。感觉到行为的电路必须包含各种神经计算，例如 那些确定感知到的线索的身份和含义、衡量内部状态、 记住以前的经验，并指挥肌肉动作。然而，在不了解全部情况的情况下 模型电路的各个部分，研究这些计算发生的位置和方式已经证明 难的。目前，大多数行为背后的完整电路结构在很大程度上是未知的，并且 小鼠边缘系统尚未遍历完整的模型电路。所以， 神经编码的研究依赖于对单个大脑区域的研究，例如大脑的细分 杏仁核或下丘脑。这种专注可能类似于盲人触摸物体的不同部分。 大象;如果不了解整体，解释可能会被扭曲。在这里我们建议 从感觉到动机行为需要使用整个回路，并且将其作为一个整体进行研究 加速理解。我们将通过系统控制来克服这个瓶颈 小鼠的嗅觉系统引发尿液标记行为作为理想的模型电路。之上 雄性老鼠闻到雌性老鼠的气味后，会故意在其身上留下大量尿痕。 宣传他们的性行为。为了研究这个激励电路如何编码行为， 我们将 1) 识别出一个完整的、从感觉到肌肉、产生行为的解剖回路，2) 确定与行为相关的相关神经元的活动模式并 彼此，以及3）确定整个电路的神经逻辑，该电路集成了内部状态和 经验。完成这些目标将提供一个统一的图景，说明简单的动机如何 行为在大脑中被编码。我们期望它也能提供实验手段 识别并分配基本已知和意外原则的顺序和结构 信息从最初的嗅觉传播时如何被表示、改变和整合 感觉到最终的肌肉活动。一旦完成，方法和结果 知识将为我们和其他人提供解决方案，用作机械论的模板 研究其他更复杂的动机回路中的感觉到行为的逻辑。我们 预计对完整电路的部件和活动模式的充分了解将提供 了解感觉系统、大脑和身体如何共同发挥作用的关键的第一步 产生行为。