Simultaneous Analysis of Neurochemical and Behavioral/Cognitive Events In Vivo

体内神经化学和行为/认知事件的同步分析

• 批准号: 7874363
• 负责人: Michael A. Johnson
• 金额: $ 20.11万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7874363
• 关键词: Addictive Behavior; Address; Area; Behavior; Behavioral; Behavioral Assay; Behavioral Paradigm; Brain; Cognition; Cognitive; Complex; Corpus striatum structure; Data; Decision Making; Development; Dopamine; Electrodes; Environment; Event; Floor; Flowers; Gilles de la Tourette syndrome; Goals; Health; Human; Huntington Disease; Hybrids; Impaired cognition; Ingestion; Investigation; Knowledge; Laboratory Scientists; Learning; Legal patent; Measurement; Measures; Mental Depression; Methodology; Methods; Mission; Monitor; Motor; Movement; Movement Disorders; Neurobiology; Neurodegenerative Disorders; Neurologic; Neuromodulator; Neurosciences; Neurotransmitters; Nucleus Accumbens; Obsessive-Compulsive Disorder; Parkinson Disease; Play; Procedures; Psychological reinforcement; Public Health; Rattus; Research; Research Design; Research Personnel; Resolution; Rewards; Rodent; Role; Scanning; Signal Transduction; Societies; Techniques; Time; Training; Uncertainty; Work; Yin; addiction; awake; base; behavior measurement; carbon fiber; cognitive function; design; disability; dopamine system; empowered; expectation; extracellular; in vivo; innovation; insight; instrument; neglect; nervous system disorder; neurochemistry; novel strategies; programs; public health relevance; research study; response; sequence learning; theories; uptake

DESCRIPTION (provided by applicant): The use of fast scan cyclic voltammetry (FSCV) in conjunction with discrete behavioral events, such as learned lever presses, has proven to be a useful approach for studies of addiction and reward-based learning. Nevertheless, it neglects behavioral events that occur between lever presses and is limited in that the occurrence of many behaviors may not be identifiable by unaided human observation, placing a fundamental limitation on how much neurochemical information can be attributed to behaviors. Therefore, there is a critical need to develop an approach capable of correlating subtle movement with neurochemical measurements. The long-term goal is to develop methods that facilitate researchers' efforts to understand brain function. The central aim of this proposal is to advance the ability of laboratory scientists to correlate brain DA transients with ongoing behavior by combining FSCV with high-resolution behavioral methods. The rationale is that integration of FSCV with the force-plate actometer, which is capable of objectively measuring subtle rodent movements on temporally compatible timescales, will empower investigators to combine FSCV measurement with more complex, and more informative, behavioral assays. To facilitate the use of this integrated approach for complex cognitive/behavioral paradigms, a hybrid operant chamber with a force-plate actometer as its floor will be used to study the differential reinforcement of low rates behavioral paradigm while collecting FSCV data. Because the proposed methods will help bridge the gap between motor and cognitive function and neurochemistry, it will have broad applicability to many areas of research including, but not limited to: (1) fundamental neurobiological studies of dopamine signaling and behavior/cognition; (2) dopamine-related movement disorders [e.g. Huntington's disease (HD), Parkinson's disease (PD), Tourette's syndrome (TS)]; (3) studies of addiction and compulsion; and (4) mechanisms of action of CNS-active pharmacological agents. Thus, the proposed research is relevant to that part of NIH's mission pertaining to the development of fundamental knowledge that will potentially help reduce the burdens of human illness and disability. The central aim will be accomplished by completion of the following two specific aims: (1) Apply a combined behavioral/voltammetric paradigm for monitoring sub-second behaviors and corresponding neurochemical changes associated with reward expectation and delivery and (2) Apply the combined behavioral/voltammetric methodology to measure dopamine transients associated with self-initiated behaviors. This combined, high time resolution approach is innovative because it is the first approach to make use of simultaneous high temporal resolution neurochemical and behavioral measurements in a complex cognitive task. The proposed research is significant because it will expand the ability of neuroscientists to correlate brain dopamine system functions with learned, motivated rodent behaviors and thereby provide new information fundamental to understanding a range of health problems in which dopamine plays a role. PUBLIC HEALTH RELEVANCE: The proposed studies are designed to enhance the ability of investigators to conduct in vivo experiments aimed at resolving how sub-second alterations in extracellular dopamine levels impact subtle and complex cognitive behaviors. The proposed research has relevance to public health because this approach can be applied towards unraveling the underlying mechanisms associated with dopamine-related neurological disorders.

描述（由申请人提供）：快速扫描循环伏安法（FSCV）与离散行为事件（例如习得的杠杆按下）的结合使用已被证明是研究成瘾和基于奖励的学习的有用方法。 然而，它忽略了按下杠杆之间发生的行为事件，并且受到限制，因为许多行为的发生可能无法通过人类的独立观察来识别，从而对有多少神经化学信息可以归因于行为产生了根本的限制。 因此，迫切需要开发一种能够将细微运动与神经化学测量相关联的方法。 长期目标是开发有助于研究人员了解大脑功能的方法。 该提案的中心目标是通过将 FSCV 与高分辨率行为方法相结合，提高实验室科学家将大脑 DA 瞬变与持续行为关联起来的能力。 其基本原理是，FSCV 与测力板活动计的集成能够在时间兼容的时间尺度上客观地测量啮齿动物的细微运动，这将使研究人员能够将 FSCV 测量与更复杂、信息更丰富的行为测定结合起来。 为了便于将这种综合方法用于复杂的认知/行为范式，将使用一个以测力板测力计作为其地板的混合操作室来研究低速率行为范式的差异强化，同时收集 FSCV 数据。 由于所提出的方法将有助于弥合运动和认知功能与神经化学之间的差距，因此它将广泛适用于许多研究领域，包括但不限于：（1）多巴胺信号传导和行为/认知的基础神经生物学研究； (2) 多巴胺相关的运动障碍[例如 亨廷顿病（HD）、帕金森病（PD）、抽动秽语综合征（TS）]； (3) 成瘾和强迫研究； (4)中枢神经系统活性药物的作用机制。 因此，拟议的研究与 NIH 使命的一部分相关，即发展基础知识，这将有可能有助于减轻人类疾病和残疾的负担。 中心目标将通过完成以下两个具体目标来实现：（1）应用组合的行为/伏安范式来监测亚秒级行为以及与奖励期望和交付相关的相应神经化学变化；（2）应用组合的行为/伏安范式。伏安法测量与自发行为相关的多巴胺瞬变。 这种组合的高时间分辨率方法具有创新性，因为它是第一种在复杂的认知任务中同时使用高时间分辨率神经化学和行为测量的方法。 这项研究意义重大，因为它将扩大神经科学家将大脑多巴胺系统功能与习得的、有动机的啮齿动物行为联系起来的能力，从而为理解多巴胺发挥作用的一系列健康问题提供基础的新信息。 公共健康相关性：拟议的研究旨在增强研究人员进行体内实验的能力，旨在解决细胞外多巴胺水平的亚秒级变化如何影响微妙和复杂的认知行为。 拟议的研究与公共卫生相关，因为这种方法可以应用于揭示与多巴胺相关的神经系统疾病相关的潜在机制。