Spatiotemporal dynamics of striatal dopamine release in reinforcement learning

描述(由申请人提供)：经典条件作用可以说是我们拥有的使我们的行为适应不断变化的环境的最基本的工具。食欲经典条件反射可以被认为是在强化和环境中的刺激之间建立一种习得的联系的过程，环境中的刺激标志着它的可用性。这种形式的“强化学习”为生物体提供了一种有效的手段，可以使用预测性信息来塑造和指导准备行动，从而努力获得最大的回报。在过去的三十年里，我们对强化学习背后的神经生物学机制的理解取得了重大进展。特别是，多巴胺神经元中神经元活动的短时相性爆发，被认为会在整个纹状体产生细胞外多巴胺浓度的快速和瞬时增加，作为自然和药物奖励强化过程的必要组成部分，受到了相当大的关注。儿茶酚胺研究的中心教条认为，多巴胺的传输是以统一的广播信号从中脑到前脑的所有目标结构进行的。然而，越来越多的证据表明，在学习过程的不同阶段，纹状体内的不同核团可能会收到不同的信号，以响应初级奖赏和条件线索。假设多巴胺信号在动力学和稳定性上的这种区域特异性对应于多巴胺在这些结构中可能在学习和行为控制中扮演的主要分离的角色。目前的提案将用三个具体目标来检验这些假设。目的1将研究学习历史和任务的特定特征对腹侧纹状体中相多巴胺稳定性的影响。目的2将检测在学习的不同阶段，相多巴胺对纹状体激活的影响，并评估行为的一致区域控制。目标3将检测强化学习的多个阶段(获得、延长训练和消退)中腹侧和背侧纹状体中多巴胺的时相释放，目的是将特定行为的发展与每个结构中的时相信号特征进行关联和比较。

DESCRIPTION (provided by applicant): Classical conditioning is arguably the most fundamental tool we possess for adapting our behavior to a changing environment. Appetitive classical conditioning can be thought of as the process that establishes a learned association between reinforcement and the stimuli in the environment that signal its availability. This form of "reinforcement learning" provides organisms with a potent means to use predictive information to mold and guide preparatory action in an effort to maximize reward. The past three decades have been marked by major advances in our understanding of the neurobiological mechanisms that underlie reinforcement learning. In particular, short "phasic" bursts of neuronal activity in dopamine neurons, which are thought to produce rapid and transient increases in extracellular dopamine concentration throughout the striatum, have received considerable attention as a necessary component of the reinforcement process for both natural and drug reward. The central dogma in catecholamine research has held that dopamine transmission proceeds as a uniform broadcast signal from the midbrain to all target structures in the forebrain. However, there is mounting evidence that separate nuclei within the striatum may receive differential signals in response to primary rewards and conditioned cues at different stages in the learning process. It is hypothesized that this regional specificity in the dynamics and stability of dopamine signaling corresponds to the largely segregated roles in both learning and behavioral control that dopamine may play in these structures. The current proposal will test these hypotheses with three specific aims. Aim 1 will examine the impact of learning history and specific features of the task on the stability of phasic dopamine in the ventral striatum. Aim 2 will examine the influence of phasic dopamine on the activation of the striatum during different stages of learning and assess the coincident regional control of behavior. Aim 3 will examine phasic dopamine release in the ventral and dorsal striatum during multiple stages of reinforcement learning (acquisition, extended training and extinction) with the goal of correlating and comparing the development of specific behaviors to the profile of phasic signaling in each structure.