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）已被认为是理解许多精神和神经疾病的重要靶点，并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。然而，这两个方面之间关系的本质是有争议的。更复杂的是，DA表现出两种不同类型的活动，相性的，爆发样的放电和强直性的起搏器样的活动。这两种类型的活动可能与动机和强化学习有不同的联系。然而，目前很难独立研究一种活动对另一种活动的贡献。在这个提议中，我们将创建两个转基因小鼠系，导致相性DA活性的改变而不影响强直活性。然后，我们将使用分离动机和强化学习的测试范式来描述这些小鼠的行为特征，以评估阶段性DA活动对两者的独立贡献。一个计算模型形式化强化学习和动机之间的假设关系，并结合相性和强直性活动将被开发