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DREADD inactivation reveals critical role of orbitofrontal cortex in reward-based adaptive decision-making in monkeys
https://repo.qst.go.jp/records/78039
https://repo.qst.go.jp/records/78039b5b0871f-b80b-46d5-ae52-d1b05379c86b
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-12-17 | |||||
| タイトル | ||||||
| タイトル | DREADD inactivation reveals critical role of orbitofrontal cortex in reward-based adaptive decision-making in monkeys | |||||
| 言語 | ||||||
| 言語 | jpn | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
小山, 佳
× 小山, 佳× 堀, 由紀子× 永井, 裕司× 平林, 敏行× 宮川, 尚久× 藤本, 敦× 三村, 喬生× 井上, 謙一× Eldridge, Mark× Saunders, Richard× 須原, 哲也× 高田, 昌彦× 樋口, 真人× Richmond, Barry× 南本, 敬史× Oyama, Kei× Hori, Yukiko× Nagai, Yuji× Hirabayashi, Toshiyuki× Miyakawa, Naohisa× Mimura, Koki× Suhara, Tetsuya× Higuchi, Makoto× Minamimoto, Takafumi |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | To survive in a dynamic world, animals must rapidly adapt to novel environments and optimize their behavior to obtain rewards. The primate orbitofrontal cortex (OFC) is thought to contribute to reward-based adaptive decision-making. However, a causal relationship has not yet been established, mainly because the reversible inactivation of large and non-continuous areas of the brain, like the bilateral OFC, is technically challenging in non-human primates. In this study, we applied the chemogenetic technique, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to reversibly inactivate OFC in macaque monkeys. Three monkeys underwent open surgery to receive multiple injections of an adeno-associated viral vectors expressing a silencing DREADD, hM4Di, into OFC bilaterally. Several weeks after the injections, we performed a positron emission tomography (PET) scan with a DREADD-selective ligand, [11C]deschloroclozapine (DCZ) and confirmed in vivo that hM4Di expression covered OFC bilaterally as intended. Reward-based adaptive decision-making was tested with a modified reversal learning task in which the monkeys were required to choose either of two visual stimuli presented on a computer screen. On each day, five new visual stimuli were paired with 1, 2, 3, 4, or 5 drops of juice. In each trial, two stimuli were randomly selected from the five. To maximize the rewards, the monkeys had to choose a better option by learning the session-specific stimulus-reward associations (learning phase). After the performance was stabilized (optimal choice >80%), the stimulus-reward associations were reversed (S1-R5, S2-R4…S5-R1). Now to maximize the reward, the monkeys had to select the previously inferior stimuli (reversal phase). After several months of training, the monkeys learned to choose a better option in both the learning and reversal phases within several tens of trials in each day’s session. Intramuscular injection of the novel DREADD agonist, DCZ, did not impair initial learning but was followed by impaired performance during the reversal in all three monkeys. This impairment is attributed to the OFC-DREADD inactivation, because the injection of DCZ alone did not affect the performance in a control monkey without DREADD expression. These results suggest that the primate OFC plays a critical role in reward-based adaptive decision-making when a situation requires overriding of the previously established associations. Support: MEXT/JSPS KAKENHI Grant Numbers JP15H05917, JP15K21742, JP18H04037 (to TM), 18K15353 (to KO), AMED Grant Numbers JP18dm0107146 (to TM) |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 第42回日本神経科学大会 | |||||
| 発表年月日 | ||||||
| 日付 | 2019-07-27 | |||||
| 日付タイプ | Issued | |||||
