Chemogenetic Disconnection between the Orbitofrontal Cortex and the Rostromedial Caudate Nucleus Disrupts Motivational Control of Goal-Directed Action

Kei Oyama, Yukiko Hori, Koki Mimura, Yuji Nagai, Mark A.G. Eldridge, Richard C. Saunders, Naohisa Miyakawa, Toshiyuki Hirabayashi, Yuki Hori, Ken Ichi Inoue, Tetsuya Suhara, Masahiko Takada, Makoto Higuchi, Barry J. Richmond, Takafumi Minamimoto

研究成果: ジャーナルへの寄稿学術論文査読

8 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)6267-6275
ページ数9
ジャーナルJournal of Neuroscience
42
32
DOI
出版ステータス出版済み - 10-08-2022
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学一般

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