Neural Mechanisms of Habit Formation and Maintenance

习惯形成和维持的神经机制

基本信息

批准号：
8529407
负责人：
Henry Yin
金额：
$ 50.58万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8529407
关键词：
AMPA Receptors Adenosine A2A Receptor Basal Ganglia Behavior Behavior Control Behavioral Brain Cells Corpus striatum structure Data Development Electrodes Exercise Feedback Genetic Genetically Modified Animals Glutamates Goals Habits Health Human Imagery Implant Knowledge Laboratory Study Lead Learning Life Style Light Maintenance Measures Mediating Mission Molecular Mus N-Methyl-D-Aspartate Receptors NMDA receptor A1 Neurons Operant Conditioning Pathway interactions Pattern Play Process Psychological reinforcement Public Health Receptor Signaling Research Resources Role Signal Transduction Slice Synaptic Transmission Synaptic plasticity Techniques Testing Time Training Work addiction awake disability genetic manipulation in vivo innovation insight learned behavior mouse model neural circuit neurobiological mechanism neuromechanism novel strategies patch clamp prevent receptor relating to nervous system research study selective expression transmission process

项目摘要

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.

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，行为控制会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。尽管已经确定了习惯形成的基本神经回路，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了解，因此很难理解潜在的神经机制。本提案将阐明习惯形成和长期维持的机制。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。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传导模式，对特定基底神经节通路中的突触可塑性和传递产生不同的影响。在小鼠模型中使用仪器调节，拟议的实验将检查对动机状态变化的敏感性以及面对反馈功能变化的持久性。该提案的主要创新特点是首次将转基因动物的定量行为分析与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面上研究习惯形成的机制。这项研究意义重大，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。所提出的实验结果可能对开发新策略产生重大影响，以促进有助于健康生活方式的行为模式。