Ensemble Activity in Rat Striatum During Habit Learning

描述（由申请人提供）：基底神经节主要参与神经系统疾病（如帕金森病）的病因学以及这些疾病中受影响的运动和认知功能。基底神经节还涉及神经精神障碍，如强迫症，其与焦虑症和抑郁症密切相关并且通常与焦虑症和抑郁症共病。了解基底神经节如何导致这样一系列的大脑疾病，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，以测试特定的假设，认知和行动导向功能的基底神经节在这种习惯性和重复性的行为。我们已经开发出一种行为模型，允许大鼠启动自愿运动，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，大规模的可塑性纹状体神经元的放电模式在程序学习。这些模式的出现是由于学习的结果，从“探索”到“利用”的行为转变。我们现在建议记录纹状体中的神经元活动，与多电极慢性记录方法，作为大鼠执行奖励为基础的任务，将不同的复杂性和奖励预期相关的任务参数，以分析特定属性的纹状体可塑性。我们建议记录穗活动和当地的场电位活动和方法的数据分析集中在三个特定的假设。通过这些研究，我们的目的是阐明基底神经节活动在学习过程中的功能特性和可塑性，这种活动在学习。总之，拟议的研究将有助于澄清涉及神经系统和神经精神疾病的皮质基底神经节环的功能。了解这些大脑回路中的活动模式是如何获得的，与了解异常活动模式是如何形成的直接相关。基底神经节中神经可塑性的这种分析因此与对一系列人类疾病的研究相关，包括帕金森氏病、亨廷顿氏病、图雷特综合征和相关的OC-谱系障碍.因此，我们认为，拟议的工作是重要的NIMH的使命，这是了解，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.