Sensory pathways for stimulus detection during behavior

行为过程中刺激检测的感觉通路

• 批准号: 9155936
• 负责人: Manuel A Castro-Alamancos
• 金额: $ 53.13万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9155936
• 关键词: Acute; Address; Animals; Behavior; Behavioral; Brain; Detection; Disease; Electrophysiology (science); Environment; Exploratory Behavior; Eye; Fingers; Goals; Habits; Head; Histology; Knowledge; Lead; Learning Disabilities; Limb structure; Mediating; Mental disorders; Methods; Motor; Movement; Neurons; Parkinson Disease; Pathway interactions; Pharmacology; Population; Positioning Attribute; Process; Research; Rodent; Role; Sensory; Sensory Neglects; Slice; Stimulus; Syndrome; Testing; Vibrissae; brain tissue; designer receptors exclusively activated by designer drugs; external ear auricle; habituation; information processing; nervous system disorder; neural circuit; novel; operation; optogenetics; relating to nervous system; response; sensor; sensory stimulus; vigilance

Summary During different behavioral states, such as quiescence versus vigilance, neural circuits are set into distinct operating modes and respond to afferent inputs, such as sensory stimulation, in very different ways. In other words, neural circuits are rapidly configured into appropriate information processing modes demanded by behavioral states. The first question this project addresses is, what are the operating modes of sensorimotor circuits during different behavioral states and how are they set? During exploratory behaviors, animals move their body (head, limbs, and trunk) and adjust the position of the sensors (eyes, fingers, pinnae, whiskers) used to explore the environment. During these states, the brain must disambiguate the neural activity that causes the movements from the activity that is driven by the movement and its interaction with the environment. The second question this project addresses is, how does the brain differentiate motor from sensory activities during active exploration of the environment? As animals explore the environment, detection of an unexpected stimulus leads to an orienting response by which animals move to evaluate the stimulus. Repeated presentation of the stimulus without significant consequences leads to habitation of the orienting response, and the stimulus is eventually ignored. The third question this project addresses is, what neural circuits drive orienting responses and how does habituation occur at a neural level? These questions will be investigated using a combination of methods that include electrophysiology, optogenetics, DREADDs, pharmacology, and histology applied using a variety of approaches ranging from acute slices of brain tissue to freely behaving rodents conducting behavioral tasks. We will take advantage of readily available Cre driver lines that allow to control the activity of specific neuronal populations and test their role in behavior. The neural and behavioral processes we study are normal, but when they go awry they lead to neurological disorders. Deciphering the normal operating modes of neural circuits is essential to understand how these operations are impacted by neurological disorders.

概括 在不同的行为状态下，例如静止与警惕，神经回路被设置为不同的操作模式，并以非常不同的方式响应传入输入，例如感觉刺激。换句话说，神经回路被快速配置成行为状态所需的适当的信息处理模式。该项目要解决的第一个问题是，不同行为状态下感觉运动电路的工作模式是什么以及它们是如何设置的？在探索行为过程中，动物会移动身体（头部、四肢和躯干）并调整用于探索环境的传感器（眼睛、手指、耳廓、胡须）的位置。在这些状态下，大脑必须区分引起运动的神经活动和由运动及其与环境相互作用驱动的活动。该项目解决的第二个问题是，在主动探索环境的过程中，大脑如何区分运动活动和感觉活动？当动物探索环境时，检测到意外刺激会导致定向反应，动物通过移动来评估刺激。重复出现刺激而没有产生重大后果，会导致定向反应的形成，刺激最终会被忽略。该项目要解决的第三个问题是，什么神经回路驱动定向反应以及神经水平上的习惯化是如何发生的？这些问题将采用多种方法进行研究，包括电生理学、光遗传学、DREADD、药理学和组织学，应用多种方法，从脑组织的急性切片到执行行为任务的自由行为的啮齿动物。我们将利用现成的 Cre 驱动线来控制特定神经元群的活动并测试它们在行为中的作用。我们研究的神经和行为过程是正常的，但当它们出错时，就会导致神经系统疾病。破译神经回路的正常操作模式对于理解神经系统疾病如何影响这些操作至关重要。