Balancing risk-return decisions by manipulating the mesofrontal circuits in primates

Author:

Sasaki Ryo1ORCID,Ohta Yasumi2ORCID,Onoe Hirotaka3,Yamaguchi Reona4,Miyamoto Takeshi15ORCID,Tokuda Takashi6ORCID,Tamaki Yuki1ORCID,Isa Kaoru1ORCID,Takahashi Jun7ORCID,Kobayashi Kenta8ORCID,Ohta Jun2ORCID,Isa Tadashi134ORCID

Affiliation:

1. Division of Physiology and Neurobiology, Department of Neuroscience, Graduate School of Medicine, Kyoto University, Kyoto-shi, Kyoto 606-8501, Japan.

2. Division of Materials Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma-shi, Nara 630-0192, Japan.

3. Human Brain Research Center, Graduate School of Medicine, Kyoto University, Kyoto-shi, Kyoto 606-8507, Japan.

4. Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto-shi, Kyoto 606-8501, Japan.

5. Japan Society for the Promotion of Science, Chiyoda-Ku, Tokyo 102-0083, Japan.

6. Institute of Innovative Research, Tokyo Institute of Technology, Meguro-Ku, Tokyo 152-8550, Japan.

7. Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto-shi, Kyoto 606-8507, Japan.

8. Section of Viral Vector Development, National Institute for Physiological Sciences, Okazaki-shi, Aichi 444-8585, Japan.

Abstract

Decision-making is always coupled with some level of risk, with more pathological forms of risk-taking decisions manifesting as gambling disorders. In macaque monkeys trained in a high risk–high return (HH) versus low risk–low return (LL) choice task, we found that the reversible pharmacological inactivation of ventral Brodmann area 6 (area 6V) impaired the risk dependency of decision-making. Selective optogenetic activation of the mesofrontal pathway from the ventral tegmental area (VTA) to the ventral aspect of 6V resulted in stronger preference for HH, whereas activation of the pathway from the VTA to the dorsal aspect of 6V led to LL preference. Finally, computational decoding captured the modulations of behavioral preference. Our results suggest that VTA inputs to area 6V determine the decision balance between HH and LL.

Publisher

American Association for the Advancement of Science (AAAS)

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