PET imaging-guided chemogenetic silencing reveals a critical role of primate rostromedial caudate in reward evaluation

Yuji Nagai, Erika Kikuchi, Walter Lerchner, Ken-ichi Inoue, Bin Ji, Mark A. G. Eldridge, Hiroyuki Kaneko, Yasuyuki Kimura, Arata Oh-Nishi, Yukiko Hori, Yoko Kato, Toshiyuki Hirabayashi, Atsushi Fujimoto, Katsushi Kumata, Ming-Rong Zhang, Ichio Aoki, Tetsuya Suhara, Makoto Higuchi, Masahiko Takada, Barry J. Richmond and Takafumi Minamimoto ()
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Yuji Nagai: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Erika Kikuchi: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Walter Lerchner: Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health
Ken-ichi Inoue: Systems Neuroscience Section, Primate Research Institute, Kyoto University
Bin Ji: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Mark A. G. Eldridge: Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health
Hiroyuki Kaneko: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Yasuyuki Kimura: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Arata Oh-Nishi: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Yukiko Hori: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Yoko Kato: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Toshiyuki Hirabayashi: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Atsushi Fujimoto: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Katsushi Kumata: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Ming-Rong Zhang: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Ichio Aoki: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Tetsuya Suhara: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Makoto Higuchi: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology
Masahiko Takada: Systems Neuroscience Section, Primate Research Institute, Kyoto University
Barry J. Richmond: Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health
Takafumi Minamimoto: National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology

Nature Communications, 2016, vol. 7, issue 1, 1-8

Abstract: Abstract The rostromedial caudate (rmCD) of primates is thought to contribute to reward value processing, but a causal relationship has not been established. Here we use an inhibitory DREADD (Designer Receptor Exclusively Activated by Designer Drug) to repeatedly and non-invasively inactivate rmCD of macaque monkeys. We inject an adeno-associated viral vector expressing the inhibitory DREADD, hM4Di, into the rmCD bilaterally. To visualize DREADD expression in vivo, we develop a non-invasive imaging method using positron emission tomography (PET). PET imaging provides information critical for successful chemogenetic silencing during experiments, in this case the location and level of hM4Di expression, and the relationship between agonist dose and hM4Di receptor occupancy. Here we demonstrate that inactivating bilateral rmCD through activation of hM4Di produces a significant and reproducible loss of sensitivity to reward value in monkeys. Thus, the rmCD is involved in making normal judgments about the value of reward.

Date: 2016
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DOI: 10.1038/ncomms13605

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