Genetic Manipulation of Phasic Dopaminergic Activity

多巴胺（DA）已被认为是理解许多精神疾病和 神经系统疾病，并被认为在成瘾中发挥核心作用。研究支持DA的作用 在激励过程和强化学习中的作用。这些之间关系的性质 然而，DA的两个方面是有争议的。更复杂的是，DA表现出两种不同的类型 的活动，阶段性，突发样放电和紧张性起搏器样活动。这两种类型的活动可能是 与动机和强化学习有着不同的联系。然而，目前很难 研究一种活动独立于另一种活动的贡献。在本提案中，我们将创建两个 转基因小鼠系，其导致阶段性DA活性的改变而不影响紧张性活性。我们 然后，我将使用测试范式对这些小鼠进行行为特征分析， 强化学习来评估阶段性DA活性对每个的独立贡献。一 一个计算模型形式化强化学习和 动机和结合阶段性和紧张性活动将得到发展。

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.