Ensemble activity in rat corticostriatal circuits during habit learning

描述（由申请人提供）：当我们重复目标导向的行为时，这些行为往往会成为习惯，以至于我们几乎可以不假思索地执行它们。这种养成习惯的能力在我们的日常生活中是非常宝贵的。当我们能以习惯模式运作时，我们释放了认知资源。目标导向的行为成为习惯的过程引起了基础科学家和医生的极大兴趣，因为当这种习惯过程出错时，行为问题就会出现。在以重复行为为主要症状的神经精神疾病中，习惯的形成可能是超速的。当我们失去形成习惯的能力时，我们的思想和行动可能会失去正常惯例赋予我们行为的部分基本组织。这项工作的目标是确定电路层面的神经机制，这种机制是从深思熟虑的行为表现到习惯性的表现模式的基础，在这种模式下，行为继续被执行，而不参考原始目标。众所周知，部分前额叶皮层和纹状体对习惯的形成是必要的，但它们如何使行为转变为习惯行为仍然不清楚。我们记录了从早期习得到过度训练形成习惯的整个过程中，前额叶皮层和纹状体的神经活动同时发生。我们发现，当目标导向行为向习惯行为转变时，纹状体不同部位和前额皮质的神经元放电模式都发生了显著变化。我们现在提议通过实验来确定这些区域是如何相互作用的，以及在老鼠形成习惯的过程中，是否存在通过干扰或沉默单个区域来控制的区域，以便了解大脑区域网络如何在灵活的目标导向行为和不那么灵活的习惯行为之间带来转变。行为的灵活性和固定性之间的平衡失调是许多神经和神经精神疾病的关键，包括帕金森病、强迫症和精神病。因此，提出的实验与NIMH了解、预防和治疗精神疾病的使命直接相关。

DESCRIPTION (provided by applicant): As we repeat goal-directed behaviors, these behaviors often become habitual and so routine that we can perform them almost without thinking. This capacity to form habits is very valuable in our normal lives. When we can operate in a habitual mode, we free up cognitive resources. The process by which goal-directed behaviors become habitual has attracted great interest among basic scientists and also among physicians, because when this habit-process goes awry, behavioral problems can emerge. In neuropsychiatric disorders in which repetitive behaviors are predominant symptoms, habit forming may be in overdrive. When we lose the ready facility to form habits, thoughts and actions may lose part of the fundamental organization that normal routines confer on our behavior. The goal of the proposed work is to identify the circuit-level neural mechanisms that underlie this transition from deliberative behavioral performance to a habitual mode of performance in which the behavior continues to be performed without reference to the original goal. It is known that parts of prefrontal cortex and the striatum are necessary for habit formation, but how they act to allow the behavioral shift to habitual behavior still are not understood. We have recorded neural activity in the prefrontal cortex and striatum simultaneously through the entire process of habit formation from early acquisition to the over-training period when the habit becomes ingrained. We have found that as the shift from goal-directed to habitual behavior occurs, there are remarkable changes in the firing patterns of neurons both in different parts of the striatum and in the prefrontal cortex. We now propose experiments to determine how these regions interact and whether there are 'controller' regions by perturbing or silencing individual zones as rats form habits, in order to understand how this network of brain regions bring about shifts between flexible goal-directed behavior and less flexible habitual behavior. Disturbances in the balance between flexibility and fixity of behavior are critical in a number of neurologic and neuropsychiatric disorders ranging from Parkinson's disease to obsessive-compulsive disorder to psychosis. Thus, the experiments proposed are directly related to the mission of the NIMH to understand, prevent and cure mental illness.