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Lookup NU author(s): Dr Mark EldridgeORCiD
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Copyright © 2022 Oyama et al. The orbitofrontal cortex (OFC) and its major downstream target within the basal ganglia-the rostromedial caudate nucleus (rmCD)-are involved in reward-value processing and goal-directed behavior. However, a causal contribution of the pathway linking these two structures to goal-directed behavior has not been established. Using the chemogenetic technology of designer receptors exclusively activated by designer drugs with a crossed inactivation design, we functionally and reversibly disrupted interactions between the OFC and rmCD in two male macaque monkeys. We injected an adeno-associated virus vector expressing an inhibitory designer receptor, hM4Di, into the OFC and contralateral rmCD, the expression of which was visualized in vivo by positron emission tomography and confirmed by postmortem immunohistochemistry. Functional disconnection of the OFC and rmCD resulted in a significant and reproducible loss of sensitivity to the cued reward value for goal-directed action. This decreased sensitivity was most prominent when monkeys had accumulated a certain amount of reward. These results provide causal evidence that the interaction between the OFC and the rmCD is needed for motivational control of action on the basis of the relative reward value and internal drive. This finding extends the current understanding of the physiological basis of psychiatric disorders in which goal-directed behavior is affected, such as obsessive-compulsive disorder.
Author(s): Oyama K, Hori Y, Mimura K, Nagai Y, Eldridge MAG, Saunders RC, Miyakawa N, Hirabayashi T, Hori Y, Inoue K-I, Suhara T, Takada M, Higuchi M, Richmond BJ, Minamimoto T
Publication type: Article
Publication status: Published
Journal: Journal of Neuroscience
Year: 2022
Volume: 42
Issue: 32
Pages: 6267-6275
Print publication date: 10/08/2022
Online publication date: 06/07/2022
Acceptance date: 05/06/2022
Date deposited: 19/02/2025
ISSN (print): 0270-6474
ISSN (electronic): 1529-2401
Publisher: Society for Neuroscience
URL: https://doi.org/10.1523/JNEUROSCI.0229-22.2022
DOI: 10.1523/JNEUROSCI.0229-22.2022
PubMed id: 35794012
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