Genetic Manipulation of Phasic Dopaminergic Activity

阶段性多巴胺能活性的基因操纵

• 批准号: 6993965
• 负责人: JEFF A. BEELER
• 金额: $ 4.4万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-11-01 至 2007-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6993965
• 关键词: behavior test; behavioral /social science research tag; behavioral genetics; dopamine; genetically modified animals; laboratory mouse; learning; motivation; neurogenetics; postdoctoral investigator; reinforcer

DESCRIPTION (provided by applicant): Dopamine (DA) has been implicated as an important target in understanding a number of psychiatric and neurological disorders and is believed to play a central role in addiction. Research supports a role for DA in both motivational processes and reinforcement learning. The nature of the relationship between these two aspects of DA, however, is controversial. Further complicating matters, DA exhibits two distinct types of activity, phasic, burst-like firing and tonic pacemaker-like activity. These two types of activity may be differentially associated with motivation and reinforcement learning. At present, however, it is difficult to study the contribution of one type of activity independently of the other. In this proposal we will create two transgenic mouse lines that result in alterations in phasic DA activity leaving tonic activity unaffected. We will then behaviorally characterize these mice using test paradigms that dissociate motivation from reinforcement learning to assess the independent contribution of phasic DA activity to each. A computational model formalizing a hypothesized relationship between reinforcement learning and motivation and incorporating both phasic and tonic activity will be developed

描述（由申请人提供）：多巴胺（DA）被认为是理解许多精神病和神经系统疾病的重要目标，并且被认为在成瘾中起着核心作用。研究支持DA在动机过程和强化学习中的作用。但是，DA这两个方面之间关系的性质是有争议的。进一步使事情变得复杂，DA表现出两种不同类型的活动，阶段性，爆发样的射击和滋补起搏器样活动。这两种类型的活动可能与动机和强化学习有所不同。然而，目前，很难独立研究一种类型的活动的贡献。在此提案中，我们将创建两种转基因小鼠系，从而导致阶段性DA活性的改变，而滋补活性不受影响。然后，我们将使用测试范式在行为上表征这些小鼠，这些范式将动机从增强学习中解散，以评估阶段性DA活动对每种活动的独立贡献。一个计算模型将形式化强化学习与动机之间的假设关系，并融入阶段性和滋补性活动