Sensory pathways for stimulus detection during behavior

行为过程中刺激检测的感觉通路

• 批准号: 10393703
• 负责人: Manuel A Castro-Alamancos
• 金额: $ 54.78万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10393703
• 关键词: Acute; Address; Animals; Behavior; Behavioral; Brain; Cre driver; 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.

摘要 在不同的行为状态，如静默和警觉，神经回路被设置为不同的操作模式，并以非常不同的方式对传入输入做出反应，例如感觉刺激。换句话说，神经电路被迅速配置成行为状态所要求的适当的信息处理模式。这个项目解决的第一个问题是，在不同的行为状态下，感觉运动电路的工作模式是什么，它们是如何设置的？在探索行为中，动物移动自己的身体(头、四肢和躯干)，并调整用于探索环境的传感器(眼睛、手指、羽毛、胡须)的位置。在这些状态下，大脑必须将引起运动的神经活动与运动及其与环境的相互作用所驱动的活动区分开来。这个项目解决的第二个问题是，在积极探索环境的过程中，大脑如何区分运动和感觉活动？当动物探索环境时，检测到意想不到的刺激会导致动物的定向反应，动物通过这种反应来评估刺激。重复呈现刺激而不产生显著后果会导致定向反应的抑制，刺激最终会被忽视。这个项目解决的第三个问题是，是什么神经回路驱动定向反应，以及习惯化是如何在神经水平上发生的？这些问题将使用包括电生理学、光遗传学、DREADDS、药理学和组织学在内的多种方法进行研究，方法范围从急性脑组织切片到执行行为任务的自由行为啮齿动物。我们将利用容易获得的CRE驱动程序线，允许控制特定神经元群体的活动，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，就会导致神经障碍。破译神经回路的正常工作模式对于了解这些操作如何受到神经障碍的影响至关重要。