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

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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.