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）：与离散的行为事件一起使用快速扫描循环伏安法（FSCV），例如Learning Lever Presses，已被证明是对成瘾和基于奖励学习的研究的有用方法。 然而，它忽略了杠杆压力机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独立的人类观察来识别，这对可以归因于行为的神经化学信息的基本限制。 因此，迫切需要开发一种能够将微妙运动与神经化学测量相关联的方法。 长期目标是开发促进研究人员了解大脑功能的努力的方法。 该提案的核心目的是通过将FSCV与高分辨率的行为方法相结合，提高实验室科学家将脑DA瞬变与持续行为相关联的能力。 基本原理是，将FSCV与力板表演计的集成能够客观地测量时间兼容的时间表上的细微啮齿动物运动，将使研究人员能够将FSCV测量与更复杂和更有信息的行为分析相结合。 为了促进这种综合方法用于复杂的认知/行为范式，带有力板表演计的混合操作室将使用其地板来研究低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功能与认知功能和神经化学之间的差距，因此它将对许多研究领域具有广泛的适用性，包括但不限于：（1）多巴胺信号传导和行为/认知的基本神经生物学研究； （2）多巴胺相关运动障碍[例如 亨廷顿氏病（HD），帕金森氏病（PD），图雷特综合症（TS）]； （3）成瘾和强迫研究； （4）CNS活性药理剂的作用机理。 因此，拟议的研究与NIH任务的那部分有关，与基本知识的发展有关，这有助于减轻人类疾病和残疾的负担。 中心目的将通过完成以下两个具体目标来实现：（1）应用行为/伏安范围的组合来监视下第二次行为以及与奖励期望和交付相关的相应神经化学变化，以及（2）应用行为/伏安方法的组合方法来测量与自我启发行为相关的多巴胺瞬变。 这种合并的高时间分辨率方法具有创新性，因为它是使用复杂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第一种方法。 拟议的研究之所以重要，是因为它将扩大神经科学家将脑多巴胺系统功能与学习，动机的啮齿动机行为相关联的能力，从而为了解多巴胺起作用的一系列健康问题提供了新的信息。 公共卫生相关性：拟议的研究旨在增强研究人员进行体内实验的能力，以解决细胞外多巴胺水平的下一步改变如何影响微妙和复杂的认知行为。 拟议的研究与公共卫生有关，因为可以将这种方法用于阐明与多巴胺相关的神经系统疾病相关的潜在机制。