Ensemble Activity in Rat Striatum During Habit Learning

描述(申请人提供)：基底节主要参与帕金森氏病等神经疾病的病因学，以及在这些疾病中受到影响的运动和认知功能。基底节还与神经精神障碍有关，如强迫症，这些疾病与焦虑症和抑郁症密切相关，而且往往是共病。了解基底神经节是如何导致这一系列脑部疾病的，对心理健康领域具有重要意义。基底节也是习惯形成和成瘾行为的神经机制的中心。我们提出了一系列协调研究，以检验关于基底节在这种习惯性和重复性行为中的认知和动作指导功能的具体假设。我们开发了一种行为模型，允许老鼠发起自愿运动，并“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，在程序性学习过程中，纹状体神经元的放电模式具有大规模的可塑性。作为学习的结果，这些模式发生在行为上从“探索”到“利用”的转变。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，因为大鼠执行基于奖赏的任务时，复杂性和与奖赏预期相关的任务参数会有所不同，以分析纹状体可塑性的特定特性。我们建议同时记录尖峰活动和局部场势活动，并以三个具体假设为重点进行数据分析。通过这些研究，我们旨在阐明学习过程中基底节活动的功能特性以及该活动在学习过程中的可塑性。总之，拟议的研究将有助于阐明皮质-基底节环在神经学和神经精神障碍中的功能。了解这些大脑回路中的活动模式是如何获得的，与理解异常活动模式是如何形成的直接相关。因此，这种对基底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、亨廷顿病、抽动症和相关的OC谱系疾病。因此，我们认为，拟议的工作对NIMH的使命--了解、预防和治疗精神疾病--具有重要意义。

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.