Genetic Manipulation of Phasic Dopaminergic Activity

阶段性多巴胺能活性的基因操纵

• 批准号: 7119031
• 负责人: JEFF A. BEELER
• 金额: $ 4.88万
• 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/7119031
• 关键词: Genetic; Manipulation; Phasic; Dopaminergic; Activity

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.

多巴胺 (DA) 已被认为是理解许多精神疾病和疾病的重要目标。 神经系统疾病被认为在成瘾中发挥着核心作用。研究支持 DA 的作用 在动机过程和强化学习中。这些之间关系的性质 然而，DA 的两个方面存在争议。更复杂的是，DA 表现出两种不同的类型 活动、阶段性、爆发式放电和强直性起搏器样活动。这两种类型的活动可能是 与动机和强化学习有不同的相关性。但目前来看，很难 研究一种活动独立于另一种活动的贡献。在此提案中，我们将创建两个 转基因小鼠品系导致阶段性 DA 活性改变，而强直活性不受影响。我们 然后将使用将动机与行为分离的测试范例来对这些小鼠进行行为特征描述 强化学习来评估阶段性 DA 活动对每个活动的独立贡献。一个 计算模型形式化了强化学习和 将发展动机并结合阶段性和补强性活动。