Neural Mechanisms of Habit Formation and Maintenance

描述(由申请人提供)：最近的研究表明，随着自愿行为的学习和重复，行为控制从目标导向和注意力模式转变为更习惯和自动的模式。这个过程被称为习惯形成，涉及控制行为的皮质-基底神经节神经回路的转变。尽管形成习惯的基本神经回路已经确定，但在我们的理解上仍然存在重大差距。特别是，促进习惯形成的条件还没有完全了解，这使得理解潜在的神经机制变得困难。本提案将阐明习惯形成和长期维持的基本机制。长期目标是了解不同的反馈模式如何改变皮质-基底节网络中的神经信号，并促进习惯的形成和维持。中心假设是，自我产生的反馈模式是习惯形成的关键决定因素。特别是，不同的反馈模式导致不同的多巴胺能信号模式，从而对特定基底节通路中突触的可塑性和传递产生不同的影响。在小鼠模型中使用工具性条件反射，拟议的实验将检验对动机状态变化的敏感性，以及面对反馈功能变化时的持久性。该方案的主要创新特征是首次将定量行为分析与体内多电极和体外全细胞膜片钳转基因动物电生理技术相结合。拟议的实验还将在多个分析层面上检查习惯形成的潜在机制。这项拟议的研究具有重要意义，因为它将阐明在环境干扰下向习惯性控制和行为自动化转变的细胞、分子和电路机制。拟议中的实验结果可能对开发促进健康生活方式的行为模式的新策略具有重要意义。

DESCRIPTION (provided by applicant): Recent work has shown that, as voluntary actions are learned and repeated, there is a shift in behavioral control from a goal-directed and attentional mode to a more habitual and automatic mode. This process is known as habit formation and involves a shift in the cortico-basal ganglia neural circuits controlling behavior. Although the basic neural circuits underlying habit formation have been identified, there remain significant gaps in our understanding. In particular, the conditions promoting habit formation are not yet fully understood, making it difficult to understand the underlying neural mechanisms. The present proposal will elucidate the mechanisms underlying habit formation as well as long-term maintenance. The long-term goal is to understand how different feedback patterns can alter neural signaling in the cortico-basal ganglia network and promote the formation and maintenance of habits. The central hypothesis is that the pattern of self-generated feedback is a critical determinant of habit formation. In particular, different feedback patterns result in different patterns of dopaminergic signaling with distinct consequences on synaptic plasticity and transmission in specific basal ganglia pathways. Using instrumental conditioning in a mouse model, the proposed experiments will examine sensitivity to changes in motivational state and persistence in the face of changes in feedback functions. The chief innovative feature of this proposal is that it combines for the first time quantitative behavioral analysis with in vivo multi-electrode and ex vivo whole-cell patch-clamp electrophysiological techniques in genetically modified animals. The proposed experiments will also examine mechanisms underlying habit formation at multiple levels of analysis. The proposed research is significant because it will shed light on the cellular, molecular, and circuit mechanisms for the transition to habitual control and behavioral automaticity in spite of environmental disturbance. Results from the proposed experiments can have significant implications for the development of novel strategies to promote behavioral patterns contributing to healthy lifestyles.