CODING OF BEHAVIORAL SEQUENCES IN THE BASAL GANGLIA

基底神经节行为序列的编码

• 批准号: 2891871
• 负责人: J Wayne Aldridge
• 金额: $ 29.05万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2891871
• 关键词: basal ganglia; dopamine agonists; ethology; experimental brain lesion; implant; injection /infusion; instinct; laboratory rat; neural information processing; psychomotor function; sensorimotor system; stereotaxic techniques; stimulus /response; substantia nigra; taste

DESCRIPTION (Adapted from applicant's abstract): The goal of this project is to understand the neuronal mechanisms of the basal ganglia that mediate sequences of behavior. Studies in humans indicate that sequence control, especially the control of movement sequences, may be a fundamental property of the basal ganglia. Motor disorders of the basal ganglia, such as Parkinson's disease and Huntington's disease, are associated with a profound loss of the ability to organize and execute sequences of movement. Furthermore, cognitive disorders of the basal ganglia such as the uncontrollable repetition of spoken words in Tourette's syndrome and the tormenting habits and thoughts of obsessive compulsive disorder suggest that sequential control mechanisms may be a fundamental property of the basal ganglia. In this project, the correlates and properties of single neurons related to instinctive, stereotyped sequences of behavioral actions will be studied. The long term goals of this project are designed to answer the following questions: How does the brain and in particular, the basal ganglia coordinate behavioral sequences? Are there basic principals for sequential organization? What are the computational properties of sequence-related neuronal assemblies in the basal ganglia? A key hypothesis to be tested in this study is that neuronal activity of a subset of cells in the basal ganglia will be related to movements within the context of rule-governed behavioral sequences and not related to these movements when they occur on their own or in irregular, less organized sets of movements. Previous experiments have shown that rats exhibit highly structured (i.e., syntactical) sequences of grooming bouts that follow strict rules for their temporal organization and that these syntactical sequences are disrupted by damage to the basal ganglia. Rats also execute comparable grooming movements in isolation and in other randomly organized patterns of movements. Our method will be to record and compare the activity of single neurons in rats during both syntactical and non-syntactical grooming sequences. It is anticipated that neuronal activity will be preferentially linked to movements in the context of stereotyped syntactical sequences. We will evaluate the anatomical location of neurons related to grooming movements to test the idea that the functional organization is related to the proposed cortico-striatal loops in the basal ganglia. We will evaluate the hypothesis that neostriatal neurons mediate sequences by modulating sensorimotor responsiveness. Finally, we will test the idea that Dl dopamine receptor activation will enhance neuronal activity related to sequential movements and the dopaminergic lesions will produce the opposite effect. It is hoped that new information about the neuronal network properties related to the organization of behavioral sequences will lead to a better understanding of the pathophysiology of basal ganglia diseases and eventually contribute to better treatments for these brain disorders.

描述(摘自申请者的摘要)：本项目的目标 是为了了解在大脑的基底节中 行为序列。对人类的研究表明，序列控制， 特别是对运动序列的控制，可能是一个基本属性 基底节的位置。基底节运动障碍，如 帕金森氏病和亨廷顿氏病，都与一种深刻的 丧失组织和执行动作序列的能力。 此外，基底节的认知障碍，如 抽动秽语综合征患者的言语失控重复 强迫症的折磨习惯和思想表明 顺序控制机制可能是基本的 神经节。在这个项目中，单个神经元的相互关系和性质 与本能的、刻板印象的行为行为序列相关的 学习。该项目的长期目标旨在回答 以下问题：大脑，尤其是基础大脑如何 神经节协调行为序列？是否有以下基本原则 按顺序组织？的计算特性是什么？ 基底节中与序列相关的神经元组装？ 这项研究中要检验的一个关键假设是， 基底节中的细胞子集将与 受规则控制的行为序列的上下文，与这些无关 当它们自己出现或以不规则的、组织较差的集合出现时 动作的变化。先前的实验表明，老鼠表现出高度的 随后的训练回合的结构化(即，句法)序列 严格的时间组织规则，以及这些句法 由于基底节受损，序列被打乱。老鼠也会杀人 在孤立和随机组织的其他组织中进行类似的梳理运动 运动的模式。我们的方法将是记录和比较 大鼠单神经元在句法和运动过程中的活动 非句法修饰序列。据预测，神经元 活动将优先与下列背景下的活动相联系 千篇一律的句法顺序。我们将评估解剖位置 与梳理动作相关的神经元来测试这一想法 功能组织与拟议的皮质-纹状体环有关 基底节。我们将评估新纹状体神经元的假设 通过调节感觉运动反应来调节序列。最后，我们 将测试DL多巴胺受体激活将增强 与顺序运动相关的神经元活动与多巴胺能 损伤会产生相反的效果。希望有新的信息 关于与组织有关的神经网络特性 行为序列将有助于更好地理解 基底节疾病的病理生理学，并最终导致 更好地治疗这些脑部疾病。