Kagoshima University · Graduate School of Medical and Dental Sciences · 教授

Research keywords大脳基底核・意思決定・運動野・神経生理・強化学習

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• Tadaaki Nishioka, Tom Macpherson, Kosuke Hamaguchi, Takatoshi Hikida . Distinct Roles of Dopamine D1 and D2 Receptor-expressing Neurons in the Nucleus Accumbens for a Strategy Dependent Decisi2021 · 記述言語： 英語 掲載種別： 研究論文（その他学術会議資料等） 出版者・発行元： Cold Spring Harbor Laboratory To optimize decision making, animals need to execute not only a strategy to choose a good option but sometimes also one to avoid a bad option. A psychological study indicates that positive and negative information is processed in a different manner in the brain. The nucleus accumbens (NAc) contains two different types of neurons, dopamine D1 and D2 receptor-expressing neurons which are implicated in reward-based decision making and aversive learning. However, little is known about the neural mechanisms by which D1 or D2 receptor-expressing neurons in the NAc contribute to the execution of the strategy to choose a good option or one to avoid a bad option under decision making. Here, we have developed two novel visual discrimination tasks for mice to assess the strategy to choose a good option and one to avoid a bad option. By chemogenetically suppressing the subpopulation of the NAc neurons, we have shown that dopamine D2 receptor-expressing neurons in the NAc selectively contribute to the strategy to avoid a bad option under reward-based decision making. Furthermore, our optogenetic and calcium imaging experiments indicate that dopamine D2 receptor-expressing neurons are activated by error choices and the activation following an error plays an important role in optimizing the strategy in the next trial. Our findings suggest that the activation of D2 receptor-expressing neurons by error choices through learning enables animals to execute the appropriate strategy. DOI： 10.1101/2021.08.05.455353
• Tadaaki Nishioka, Kosuke Hamaguchi, Satoshi Yawata, Takatoshi Hikida, Dai Watanabe . Chemogenetic Suppression of the Subthalamic Nucleus Induces Attentional Deficits and Impulsive Actio2020 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） The subthalamic nucleus (STN), a key component of the basal ganglia circuitry, receives inputs from broad cerebral cortical areas and relays cortical activity to subcortical structures. Recent human and animal studies have suggested that executive function, which is assumed to consist of a set of different cognitive processes for controlling behavior, depends on precise information processing between the cerebral cortex and subcortical structures, leading to the idea that the STN contains neurons that transmit the information required for cognitive processing through their activity, and is involved in such cognitive control directly and dynamically. On the other hand, the STN activity also affects intracellular signal transduction and gene expression profiles influencing plasticity in other basal ganglia components. The STN may also indirectly contribute to information processing for cognitive control in other brain areas by regulating slower signaling mechanisms. However, the precise correspondence and causal relationship between the STN activity and cognitive processes are not fully understood. To address how the STN activity is involved in cognitive processes for controlling behavior, we applied Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-based chemogenetic manipulation of neural activity to behavioral analysis using a touchscreen operant platform. We subjected mice selectively expressing DREADD receptors in the STN neurons to a five-choice serial reaction time task, which has been developed to quantitatively measure executive function. Chemogenetic suppression of the STN activity reversibly impaired attention, especially required under highly demanding conditions, and increased impulsivity but not compulsivity. These findings, taken together with the results of previous lesion studies, suggest that the STN activity, directly and indirectly, participates in cognitive processing for controlling behavior, and dynamically regulates specific types of subprocesses in cognitive control probably through fast synaptic transmission. DOI： 10.3389/fnsys.2020.00038 PubMed
• Kosuke Hamaguchi, Masashi Tanaka, Richard Mooney . A Distributed Recurrent Network Contributes to Temporally Precise Vocalizations . NEURON91 ( 32016 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： CELL PRESS How do forebrain and brainstem circuits interact to produce temporally precise and reproducible behaviors? Birdsong is an elaborate, temporally precise, and stereotyped vocal behavior controlled by a network of forebrain and brainstem nuclei. An influential idea is that song premotor neurons in a forebrain nucleus (HVC) form a synaptic chain that dictates song timing in a top-down manner. Here we combine physiological, dynamical, and computational methods to show that song timing is not generated solely by a mechanism localized to HVC but instead is the product of a distributed and recurrent synaptic network spanning the forebrain and brainstem, of which HVC is a component. DOI： 10.1016/j.neuron.2016.06.019 Web of Science PubMed
• 濱口 航介 . シークエンス様の神経活動と行動の神経基盤 . 生体医工学53 S98_02 - S98_02 2015年 詳細を見る 記述言語： 日本語 出版者・発行元： 一般社団法人 日本生体医工学会 Sequences of neura2015 · 記述言語： 日本語 出版者・発行元： 一般社団法人 日本生体医工学会 Sequences of neural activity are thought to play an important role in motor control. The neural mechanisms that give rise to these sequences are not well understood, but an influential idea is that activity propagation in ensembles of neurons can generate sequential activity (i.e., a synfire chain). Birdsong is an elaborate and stereotyped vocal behavior controlled with millisecond precision, and various lines of evidence support the hypothesis that song premotor neurons located in a telencephalic nucleus HVC form a synaptic chain to generate song tempo. Here we combine brain temperature manipulation, synaptic activity recording, and computational methods to show that song tempo is not generated by a local mechanism of HVC but instead is the product of a distributed and recurrent synaptic network spanning the forebrain and brainstem. Using a miniature Peltier device, we found that focally manipulating the temperature of HVC exerted much greater effect on activity propagation locally within HVC than it did on song tempo, however, exerted identical effects on song tempo and activity propagation through a recurrent network that contains HVC as one of its elements. The potential models that can account for the statistical structure of synaptic timing distribution of HVC neurons will be discussed in the talk. DOI： 10.11239/jsmbe.53.S98_02 CiNii Research

• 逆行性バーコーディングによる局所回路センサス2024 · 配分額： 13780000円 （ 直接経費： 10600000円 、 間接経費： 3180000円 ）
• 内受容感覚が行動選択を誘導する神経メカニズム2024 · 配分額： 18590000円 （ 直接経費： 14300000円 、 間接経費： 4290000円 ）
• 逆行性バーコーディングによる局所神経回路構造の解明2022 · 配分額： 9880000円 （ 直接経費： 7600000円 、 間接経費： 2280000円 ）
• 予測的価値を行動に変換する神経機構2021 · 配分額： 17940000円 （ 直接経費： 13800000円 、 間接経費： 4140000円 ） 本研究では，報酬条件が逆転する事を予期するマウスを用いて，予測に基づく価値を表現する神経細胞の同定を目指す．それらの神経活動を抑制した際，予測的な行動が抑制されるかどうか調べる事で，予測的価値を行動に変換する神経機構を明らかにする． 初年度では，予測的な行動を行う頭部拘束マウスを多数供給できる体制を確立した．具体的には，報酬１０回目で必ず報酬条件が変わる連続逆転学習課題をマウスに学習させた．もし過去の報酬履歴から行動を選択するならば，Win-Shift 選択確率（報酬が得られる行動をやめ，他の選択肢を選ぶ確率）は，ブロック内での学習が進むと低下すると予想される．実際に正答率の低い Novice マウス (正答率６０％未満)では，Win-Shift 選択確率はブロック内で低下していった．しかし正答率の高い Expert マウス (正答率７０％以上)ではブロックの後半に向けて，Win-Shift 選択確率が高まっており，ブロックの切り替わりでちょうど逆転行動を数多く行う個体が得られた．この結果は，Expert マウスが課題の構造を学習し，報酬条件の変化を予測している事を示唆している． これら予測的行動を行うマウスの前頭皮質神経細胞よりカルシウムイメージングを行ったところ，予測に基づいた価値計算を行うことを示唆する神経活動が観測された．また光遺伝学をもちいて課題遂行中に観測領域を抑制したところ，予測ができないことを示唆する行動が観測された．

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