Ensemble Activity in Rat Striatum During Habit Learning

描述（由申请人提供）：基底神经节在帕金森病等神经系统疾病的病因学以及这些疾病中受影响的运动和认知功能中起主要作用。基底神经节也与神经精神疾病有关，如强迫症，这与焦虑症和抑郁症密切相关，并常与之共病。了解基底神经节如何导致如此一系列的脑部疾病，对心理健康领域具有重要意义。基底神经节也是习惯形成和成瘾行为背后的神经机制的中心。我们提出了一系列的协调研究，以测试有关认知和行动指导功能的特定假设基底神经节在这种习惯和重复行为。我们已经开发了一种行为模型，允许老鼠发起自愿运动，并做出“决定”，是否执行一种或另一种运动模式，以获得奖励。我们的初步数据表明纹状体神经元放电模式在程序性学习过程中具有大规模的可塑性。随着学习的结果，行为从“探索”转变为“利用”，这些模式就会出现。我们现在建议用多电极慢性记录方法记录纹状体中的神经元活动，当大鼠执行基于奖励的任务时，这些任务将在复杂性和与奖励预期相关的任务参数上有所不同，以便分析纹状体可塑性的具体特性。我们建议记录尖峰活动和局部场电位活动，并针对三个具体假设进行数据分析。通过这些研究，我们旨在阐明学习过程中基底神经节活动的功能特性以及学习过程中基底神经节活动的可塑性。总之，提出的研究将有助于阐明与神经和神经精神疾病有关的皮质-基底神经节环的功能。了解这些脑回路中活动模式是如何形成的，与了解异常活动模式是如何形成的直接相关。因此，对基底神经节神经可塑性的分析与一系列人类疾病的研究相关，包括帕金森氏病、亨廷顿氏病、妥瑞氏综合征和相关的OC-谱系疾病。因此，我们认为拟议的工作对NIMH的使命很重要，NIMH的使命是了解、预防和治疗精神疾病。

DESCRIPTION (provided by applicant): The basal ganglia are centrally involved in the etiology of neurologic disorders such as Parkinson's disease and in the motor and cognitive functions that are affected in these disorders. The basal ganglia are also implicated in neuropsychiatric disorders, such as obsessive-compulsive disorder, that are closely related to and often co-morbid with anxiety disorders and depression. It is of great importance to the field of mental health to understand how the basal ganglia could contribute to such a range of brain disorders. The basal ganglia are also central to habit formation and to the neural mechanisms underlying addictive behavior. We propose a series of coordinated studies to test specific hypotheses about cognitive and action-directed functions of the basal ganglia in such habitual and repetitive behaviors. We have developed a behavioral model that allows rats to initiate voluntary movements, and to make a "decision" whether to execute one or another movement pattern in order to receive reward. Our preliminary data indicate large-scale plasticity in striatal neuronal firing patterns during procedural learning. These patterns occur as a shift occurs behaviorally from "exploration" to "exploitation" as a result of learning. We now propose to record neuronal activity in the striatum, with multi-electrode chronic recording methods, as rats perform reward-based tasks that will vary in complexity and in task parameters related to reward anticipation in order to analyze specific properties of striatal plasticity. We propose to record both spike activity and local field potential activity and to approach data analysis focusing on three specific hypotheses. Through these studies, we aim to elucidate functional properties of basal ganglia activity during learning and the plasticity of this activity during learning. Together, the proposed studies will help to clarify the function of cortico-basal ganglia loops implicated in neurologic and neuropsychiatric disorders. Understanding how patterns of activity are acquired in these brain circuits is directly relevant to understanding how abnormal patterns of activity could be laid down. Such analyses of neuroplasticity in the basal ganglia are thus relevant to work on a range of human disorders, including Parkinson's disease, Huntington's disease, Tourette syndrome and related OC- spectrum disorders. We thus believe that the proposed work is important for the mission of the NIMH, which is to understand, prevent and cure mental illness.