Neural Mechanisms of Habit Formation and Maintenance

描述（由申请人提供）：最近的研究表明，随着自主行为的学习和重复，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。虽然习惯形成的基本神经回路已经被确定，但我们的理解仍然存在重大差距。特别是，促进习惯形成的条件尚未完全理解，因此很难理解潜在的神经机制。目前的建议将阐明的机制，潜在的习惯形成以及长期的维护。长期目标是了解不同的反馈模式如何改变皮质基底神经节网络中的神经信号，并促进习惯的形成和维持。核心假设是，自我生成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多巴胺能信号传导的不同模式，对特定基底神经节通路中的突触可塑性和传递具有不同的后果。在小鼠模型中使用工具性条件反射，拟议的实验将检查对动机状态变化的敏感性和面对反馈功能变化的持久性。该提案的主要创新特征是，它首次将定量行为分析与转基因动物体内多电极和离体全细胞膜片钳电生理技术相结合。拟议的实验还将在多个分析层次上研究习惯形成的潜在机制。这项研究具有重要意义，因为它将揭示在环境干扰下向习惯性控制和行为自动性过渡的细胞、分子和电路机制。从拟议的实验结果可以有显着的影响，新的策略，以促进健康的生活方式的行为模式的发展。

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.