Genetic Manipulation of Phasic Dopaminergic Activity

多巴胺(DA)被认为是了解许多精神和心理疾病的重要靶点。 神经紊乱，被认为在成瘾中起着核心作用。研究支持发展议程的作用 无论是在激励过程中还是在强化学习中。它们之间的关系的性质 然而，DA的两个方面是有争议的。更复杂的是，DA表现出两种截然不同的类型 活动、相位性、爆发式放电和紧张性起搏器样电活动。这两类活动可能是 与动机和强化学习有不同的联系。然而，目前很难做到 独立于另一类活动，研究一类活动的贡献。在本提案中，我们将创建两个 转基因小鼠品系导致DA活动时相改变，使紧张性活动不受影响。我们 然后会使用测试范例来描述这些小鼠的行为特征 强化学习评估阶段DA活动对每个阶段的独立贡献。一个 将强化学习和强化学习之间的假设关系形式化的计算模型 将发展动力，并将阶段性和补充性活动结合起来。

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.