Genetic Manipulation of Phasic Dopaminergic Activity

描述(由申请人提供)：多巴胺(DA)被认为是了解一些精神和神经障碍的重要靶点，并被认为在成瘾中发挥核心作用。研究支持DA在激励过程和强化学习中的作用。然而，发展议程的这两个方面之间的关系的性质是有争议的。更复杂的是，DA表现出两种不同类型的活动，即相性、爆发式放电和紧张性起搏样活动。这两种活动可能与动机和强化学习有不同的联系。然而，目前很难独立于另一种活动来研究一种活动的贡献。在这项提议中，我们将创建两个转基因小鼠系，它们导致DA相活性的改变，而紧张性活动不受影响。然后，我们将使用将动机从强化学习中分离出来的测试范式来描述这些小鼠的行为特征，以评估阶段DA活动对每个阶段的独立贡献。将开发一个计算模型，该模型正式确定强化学习和动机之间的假设关系，并将阶段性和紧张性活动结合在一起。

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