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

这项拟议的研究试图为大脑在处理与奖惩相关的信息时是如何组织的，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、基本上分离的、按照对抗原则运作的电路。例如，运动(去/不去)、睡眠/清醒和恐惧反应的控制，涉及到两条不同的神经通路的激活，导致相反的结果。关于环境中奖惩相关线索的处理是由共同的神经回路还是由单独的对手通路调节的问题，目前存在很大争议，这也是拟议的研究计划的主旨。该计划将采用多学科方法，使用大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，以实现以下目标：1)描绘调节奖惩线索的皮质-边缘-纹状体回路的功能；2)识别皮质-边缘-纹状体回路中整合奖惩相关线索的离散亚域；以及3)研究神经调节(多巴胺和去甲肾上腺素)对目标行为奖惩线索控制的影响。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不断变化的激励值的基本理解提供概念上的进步。此外，这项基础研究将对大脑病理产生重要的见解，这可能会导致心理障碍，其中激励线索的处理可能会异常。

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.