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（改编自申请人的摘要）：本项目的目标 是了解基底神经节的神经机制， 行为的序列。 对人类的研究表明，序列控制， 尤其是对运动顺序的控制，可能是一个基本的属性， 基底神经节 基底神经节运动障碍，例如 帕金森氏病和亨廷顿氏病，与一种深刻的 丧失组织和执行运动序列的能力。 此外，基底神经节的认知障碍，如 在图雷特综合征中无法控制的重复说话， 强迫症的痛苦习惯和想法表明， 顺序控制机制可能是基础药物的基本性质 神经节 在这个项目中，单个神经元的相关性和特性 与本能的、刻板的行为序列相关的行为， 研究了 该项目的长期目标旨在回答 以下问题：大脑，特别是基底神经， 神经节协调行为序列 是否有基本原则， 有序组织？ 的计算性质是什么 序列相关的神经元组装在基底神经节？ 在这项研究中要检验的一个关键假设是， 基底神经节中的细胞亚群将与基底神经节内的运动有关。 规则支配的行为序列的上下文，与这些 运动时，他们发生在自己或在不规则的，较无组织的集 的运动。 以前的实验表明，老鼠表现出高度的 结构化（即，句法上）一系列的梳理动作 严格的时间组织规则， 序列被基底神经节的损伤破坏。 老鼠也执行 类似的梳理运动在隔离和其他随机组织 运动模式 我们的方法是记录和比较 大鼠单个神经元在句法和 非语法修饰序列。 据估计，神经元 活动将优先与以下背景下的运动联系起来： 刻板的句法序列 我们会评估解剖位置 与梳理动作相关的神经元，以测试这种想法， 功能组织与皮质-纹状体环有关， 基底神经节 我们将评估新纹状体神经元 通过调节感觉运动反应来调节序列。 最后我们 将测试D1多巴胺受体激活将增强D1多巴胺受体激活的想法。 与连续运动相关的神经元活动和多巴胺能神经元活动 损伤将产生相反的效果。 希望新的信息 关于神经元网络的特性， 行为序列将导致更好地理解 基底神经节疾病的病理生理学，并最终有助于 更好的治疗方法