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

这项拟议中的研究旨在提供关键和基本的见解，以了解大脑在处理与奖励和惩罚有关的信息时是如何组织的，以及这些信息如何影响决策。哺乳动物大脑中回路组织的一个显著特征是存在专门的、大部分隔离的回路，这些回路根据顺应性原则运行。例如，对运动（去/不去）、睡眠/觉醒和恐惧反应的控制涉及两种不同的神经通路的激活，导致相反的结果。环境中与奖励和惩罚相关的线索的处理是否由共同的神经回路或单独的对立通路介导的问题目前正处于激烈的争论之中，这也是拟议中的研究计划的主旨。该计划将采用多学科方法，使用脑内药理学技术以及光遗传学方法与新型大鼠行为模式相结合，以实现以下目标：1）描绘介导奖励和/或惩罚线索的功能性皮质-边缘-纹状体回路，2）识别整合奖励和惩罚相关线索的皮质-边缘-纹状体回路内的离散子域，（3）探讨神经调节因子（多巴胺和去甲肾上腺素）对目标导向行为的奖赏和惩罚线索控制的调节作用。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环境刺激的激励值变化的基本理解提供概念上的进步。此外，这一基础研究将产生重要的见解，大脑病理学可能会引起心理障碍，其中的激励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.