Gen Ohtsuki Lab
これまで、京都大学大学院医学研究科 創薬医学講座の特定教授として、脳の炎症と精神疾患発症機序の究明を目指し、げっ歯類とヒトでの精神障害の回復を目指す研究を行ってきました。2025年度からは、高次脳科学講座 神経生物学分野やシステム神経薬理学分野にて、神経変性疾患と精神疾患に関するマウスモデルとヒト病態の機序解明と回復法の開発に取り組んでいます。
研究手法は、電気生理学的手法（多細胞パッチクランプ、樹状突起記録、シナプス伝達、膜興奮性、長期可塑性など、脳切片下の記録）と in vivo 電気生理学記録、イメージング（共焦点顕微鏡、二光子顕微鏡、超解像顕微鏡、小動物核磁気画像法（fMRI））、ミクログリア解析、げっ歯類での行動実験、光・薬理遺伝学的操作、大規模データ解析（細胞レベルイメージングデータ、深層学習、生成AI、ヒトコホートデータ解析（安静時MRI）、超多重抗体染色（空間プロテオミクス）、RNA空間解析、Proteomics空間解析、ATAC-seq、Patch-seqなど）を行っています。他に、細胞レベル数理モデルシミュレーションなども行っています。現在はマルチオミクスと細胞種特異的遺伝子改変を用いた精神疾患と神経変性疾患のプログラミング解析や人工知能を使った解析および治療法開発を目指しています。特に小脳と脳免疫の機能連関に興味があります。対象疾患は、精神疾患（発達障害や統合失調症）と神経変性疾患（ALSおよびアルツハイマー型認知症）とします。
尊敬する多くの先生方の背中を見て、日々チームの皆で研究開発に精励しております。世界中の疾患に苦しまれる多くの方々の力になる研究開発を推進させます。変わらぬご指導ご鞭撻のほど戴けましたら、幸甚にございます。
依頼のご相談、ご質問など、お気軽にお問い合わせください。
As a Professor (Program-specific) of the Department of Drug Discovery Medicine at the Graduate School of Medicine, Kyoto University, I have been conducting research aimed at elucidating the mechanisms underlying neuroinflammation and the onset of psychiatric disorders, with the ultimate goal of promoting recovery from mental illness in both rodents and humans.
Starting in the 2025 academic year, I have joined the Division of Neurobiology within the Department of Cognitive and Behavioral Sciences. Here, I am engaged in research focusing on elucidating the mechanisms of neurodegenerative and psychiatric disorders using mouse models and human pathology, as well as developing novel therapeutic strategies.
Our methodologies include electrophysiological techniques (such as multi-cell patch-clamp recordings, dendritic recordings, synaptic transmission analysis, membrane excitability, and long-term plasticity in brain slices), in vivo electrophysiological recordings, imaging techniques (including confocal, two-photon, and super-resolution microscopy, as well as small animal fMRI), microglial analysis, behavioral experiments in rodents, opto- and pharmacogenetic manipulations, and large-scale data analyses (including cellular-level imaging data, deep learning, generative AI, human cohort data analysis using resting-state MRI, highly multiplexed antibody staining for spatial proteomics, spatial transcriptomics, and Patch-seq). Additionally, we have conducted simulations using mathematical modeling at the cellular level.
Currently, we are aiming to develop new approaches for understanding and treating psychiatric and neurodegenerative disorders by integrating multi-omics data and cell type–specific genetic modifications, alongside AI-based analysis and therapeutic development. In particular, we are deeply interested in the functional interaction between the cerebellum and brain immune systems.
Guided and inspired by the many distinguished researchers I deeply respect, I work diligently with my team to advance our research and development. It is my sincere hope that our work will one day contribute to alleviating the suffering of people affected by brain disorders worldwide. I would be most grateful for your continued guidance and support.
Our Publications
【original papers】
(ref. 26) Maternal immune activation followed by peripubertal stress combinedly produce reactive microglia and confine cerebellar cognition.. Hikosaka M, Parvez MSA, Yamawaki Y, Oe S, Liang Y, Wada Y, Hirahara Y, Koike T, Imai H, Oishi N, Schalbetter SM, Kumagai A, Yoshida M, Sakurai T, Kitada M, Meyer U, Narumiya S, Ohtsuki G.
Commun Biol. 2025 Mar 3;8(1):296. doi: 10.1038/s42003-025-07566-2.
(ref. 25) Sustained antidepressant effects of ketamine metabolite involve GABAergic inhibition-mediated molecular dynamics in aPVT glutamatergic neurons.
*Kawatake-Kuno A, *Li H, *Inaba H, Hikosaka M, Ishimori E, Ueki T, Garkun Y, Morishita H, Narumiya S, Oishi N, †Ohtsuki G, Murai T, †Uchida S.
Neuron. 2024 Feb 19:S0896-6273(24)00049-7. doi: 10.1016/j.neuron.2024.01.023.
(ref. 24) Editorial: Cerebellum-Related Learning and Psychiatric Diseases.
*†Gen Ohtsuki, †Taegon Kim, †Peng Sun, †Yongjun Chen, †Egidio Ugo D‘Angelo
Front Cell Neurosci. 2023 Feb 13;17:1132286. doi: 10.3389/fncel.2023.1132286
(ref. 23) Immune-Triggered Forms of Plasticity Across Brain Regions.
*Momoka Hikosaka, *Takeo Kawano, Yayoi Wada, Tomoki Maeda, Takeshi Sakurai, †Gen Ohtsuki
Front Cell Neurosci. 2022 Jul 22;16:925493. doi: 10.3389/fncel.2022.925493
(ref. 22) Acute cerebellar inflammation and related ataxia: mechanisms and pathophysiology.
*Md Sorwer Alam Parvez, †Gen Ohtsuki
Brain Sciences, 2022 Mar 10;12(3):367. doi: 10.3390/brainsci12030367
(ref. 21) Microglia-triggered hypoexcitability plasticity of pyramidal neurons in the rat medial prefrontal cortex.
*Yuki Yamawaki, *Yayoi Wada, Sae Matsui, †Gen Ohtsuki (*, equal contribution)
Current Research in Neurobiology, Volume 3, 2022, 100028. Doi: 10.1016/j.crneur.2022.100028
(ref. 20) Insights from a computational analysis of the SARS-CoV-2 Omicron variant: Host-pathogen interaction, pathogenicity and possible therapeutics.
*Md Sorwer Alam Parvez, Manash Kumar Saha, Md. Ibrahim, Yusha Araf, Md. Taufiqul Islam, †Gen Ohtsuki, †Mohammad Jakir Hosen
Immun Inflamm Dis. 2022 Jul;10(7):e639. doi: 10.1002/iid3.639
(ref. 19) High permeability of the CSF flow in the juvenile mouse brain by brain-wide DCE-MRI. [category: research paper]
*Yayoi Wada, Hirohiko Imai, Yuki Yamawaki, Md Sorwer Alam Parvez, Sae Matsui, †Gen Ohtsuki
bioRxiv. doi: https://doi.org/10.1101/2021.09.21.461189
(ref. 18) Psychosis symptoms following aberrant immunity in the brain.
*Akitoshi Ozaki, *Yuki Yamawaki, †Gen Ohtsuki.
Neural Regeneration Research, 2021 Mar;16(3):512-513. doi: 10.4103/1673-5374.293148
(ref. 17) A Destruction Model of the Vascular and Lymphatic Systems in the Emergence of Psychiatric Symptoms.
*Kohei Segawa, *Yukari Blumenthal, Yuki Yamawaki, †Gen Ohtsuki.
Biology, 10(1), 34; 13 Jan 2021, doi.org/10.3390/biology10010034
(ref. 16) Synergistic excitability plasticity in cerebellar functioning.
*†Ohtsuki G, Shishikura M, Ozaki A.
The FEBS Journal, 2020 Nov;287(21):4557-4593. doi: 10.1111/febs.15355
(This paper was selected to the cover issue.)
(ref. 15) Modification of synaptic-input clustering by intrinsic excitability plasticity on cerebellar Purkinje cell dendrites.
*†Ohtsuki G.
Journal of Neuroscience, Volume 40, 267-282, 8 Jan 2020. doi: 10.1523/JNEUROSCI.3211-18.2019
(ref. 14) Microglia-triggered plasticity of intrinsic excitability modulates psychomotor behaviors in acute cerebellar inflammation.
*Yamamoto M, *Kim M, *Imai H, Itakura Y, †Ohtsuki G.
Cell Reports, Volume 28, 2923-2938.e8, 10 Sep 2019. doi: 10.1016/j.celrep.2019.07.078
(This paper was selected to the cover issue.)
(This study was selected to the Press Conference Abstract in the Society for Neuroscience, USA, in Chicago, 2019, October 19-23rd. The selection rate is ~ 50 / 14,000+ Quite rare from Asian counties.)
(ref. 13) Synaptic Potential and Plasticity of an SK2 Channel Gate Regulate Spike Burst Activity in Cerebellar Purkinje Cells.
*Ohtsuki G, †Hansel C.
iScience, Volume 1, 49-54, 23 Mar 2018. doi: 10.1016/j.isci.2018.02.001
(This paper was selected to the cover issue.)
(ref. 12) Activity-Dependent Plasticity of Spike Pauses in Cerebellar Purkinje Cells.
*Grasselli G, He Q, Wan V, Adelman JP, Ohtsuki G, †Hansel C.
Cell Reports, Volume 14, Issue 11, 2546-2453, 22 Mar 2016. doi: 10.1016/j.celrep.2016.02.054
(ref. 11) The spontaneous ataxic mouse mutant tippy is characterized by a novel Purkinje cell morphogenesis and degeneration phenotype.
*Shih EK, Sekerková G, Ohtsuki G, Aldinger KA, Chizhikov VV, Hansel C, Mugnaini E, †Millen KJ.
Cerebellum, Volume 14, Issue 3, 292-307, Jun 2015. doi: 10.1007/s12311-014-0640-x
(ref. 10) SK2 channel modulation contributes to compartment-specific dendritic plasticity in cerebellar Purkinje cells. [category: research paper]
*Ohtsuki G, Piochon C, Adelman JP, †Hansel C.
Neuron, Volume 75, Issue 1, 108-120, 12 Jul 2012. doi: 10.1016/j.neuron.2012.05.025
(ref. 9) Similarity of visual selectivity among clonally related neurons in visual cortex. [category: research paper]
*Ohtsuki G, *Nishiyama M, *Yoshida T, Murakami T, Histed M, †Lois C, †Ohki K. (*, equal contribution)
Neuron, Volume 75, Issue 1, 65-72, 12 Jul 2012. doi: 10.1016/j.neuron.2012.05.023
(ref. 8) Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum.
*Piochon C, Levenes C, Ohtsuki G, †Hansel C.
Journal of Neuroscience, Volume 30, Issue 45, 15330-15335, 10 Nov 2010. doi: 10.1523/JNEUROSCI.4344-10.2010
(ref. 7) Intrinsic plasticity complements long-term potentiation in parallel fiber input gain control in cerebellar Purkinje cells.
*Belmeguenai A, Hosy E, Bengtsson F, Pedroarena C, Piochon C, Teuling E, He Q, Ohtsuki G, De Jeu M, Elgersma Y, De Zeeuw CI, Jörntell H, †Hansel C.
Journal of Neuroscience, Volume 30, Issue 41, 13630-13643, 13 Oct 2010. doi: 10.1523/JNEUROSCI.3226-10.2010
(ref. 6) Purkinje cell-specific knockout of PP2B impairs potentiation and cerebellar motor learning.
*Schonewille M, Belmeguenai A, Koekkoek SK, Houtman SH, Boele HJ, van Beugen BJ, Gao Z, Badura A, Ohtsuki G, Amerika WE, Hosy E, Hoebeek FE, Elgersma Y, Hansel C, †De Zeeuw CI.
Neuron, Volume 67, Issue 4, 618-628, 26 Aug 2010. doi: 10.1016/j.neuron.2010.07.009
(ref. 5) Climbing fiber signaling and cerebellar gain control.
*Ohtsuki G, Piochon C, †Hansel C.
Frontiers in Cellular Neuroscience, Volume 3, Issue 4, 1-5, 6 July 2009. doi: 10.3389/neuro.03.004.2009 [IF 6.147]
これまでの取り組み
わたしたちは脳の炎症がもたらす精神疾患発症機序と神経変性疾患機序の解明を目指し、治療法や治療薬の探索と開発を進展させます。
（現在準備中です）