Delineating cortico-limbic-striatal circuits in reward and punishment: segregation and integration

拟议的研究旨在为大脑如何组织处理与奖励和惩罚有关的信息以及这些信息如何影响决策提供关键和基本的见解。哺乳动物大脑中电路组织的一个显著特征是存在专门的、很大程度上隔离的电路，这些电路按照对立原则运作。例如，对运动（走/不走）、睡眠/清醒和恐惧反应的控制，涉及到两种截然不同的神经通路的激活，导致相反的结果。环境中奖惩相关线索的处理是由共同的神经回路还是单独的对立通路介导的，这个问题目前存在很多争论，也是拟议研究计划的主要内容。该计划将采用多学科方法，利用脑内药理学技术，以及光遗传学方法结合新的大鼠行为范式，实现以下目标：1)描述皮质-边缘-纹状体回路调节奖励和/或惩罚线索的功能；2)识别皮质-边缘-纹状体回路中整合奖励和惩罚相关线索的离散子域；3)研究神经调节剂（多巴胺和去甲肾上腺素）对奖惩线索控制对目标导向行为的调节作用。这项研究的结果将为我们对哺乳动物大脑如何协调有效的行为适应不断变化的环境刺激的激励值的基本理解提供概念上的进展。此外，这项基础研究将对可能引起心理障碍的脑病理学产生重要的见解，其中刺激线索的处理可能是异常的。

The proposed research seeks to provide critical and fundamental insights into how the brain is organized in processing information pertaining to reward and punishment, and how such information can impact decision making. One notable feature of circuit organization in the mammalian brain is the existence of dedicated, largely segregated circuits that operate on the principle of opponency. The control of movement (go/no go), sleep/wakefulness, and fear responses, for instance, involves the activation of two distinct neural pathways resulting in opposite outcomes. The question of whether the processing of reward- and punishment- related cues in the environment is mediated by a common neural circuit, or separate, opponent pathways is presently under much debate, and is the main thrust of the proposed research program. The program will adopt a multidisciplinary approach, using intra-cerebral pharmacological techniques, as well as optogenetic methods in combination with novel rat behavioural paradigms, to achieve the following objectives: 1) to delineate functional cortico-limbic-striatal circuits mediating reward and/or punishment cues, 2) to identify discrete subdomains within the cortico-limbic-striatal circuitry that integrates reward and punishment-related cues, and 3) to investigate the role of neuromodulatory (dopamine and noradrenaline) influences upon the regulation of reward- and punishment cue control over goal-directed behaviour. The outcome of this research will offer conceptual advances to our basic understanding of how the mammalian brain orchestrates effective behavioural adaptation to changing incentive values of environmental stimuli. Furthermore, this basic research will generate important insights into the brain pathology that may give rise to psychological disorders in which the processing of incentive cues may be aberrant.