Whole brain imaging of C. elegans to reveal the neural basis of exploratory navigation

• Project Area: Systems Science of Bio-navigation
• Project/Area Number: 16H06545
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: Nagoya City University (2017-2021); Osaka University (2016)
• Principal Investigator: Kimura Kotaro 名古屋市立大学, 大学院理学研究科, 教授 (20370116)
• Co-Investigator(Kenkyū-buntansha): 石原 健 九州大学, 理学研究院, 教授 (10249948)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥87,750,000 (Direct Cost: ¥67,500,000、Indirect Cost: ¥20,250,000); Fiscal Year 2020: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000); Fiscal Year 2019: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2018: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2017: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2016: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
• Keywords: 行動 / イメージング / 深層学習 / 機械学習 / 脳・神経 / ナビゲーション / 神経活動 / 神経科学

Outline of Final Research Achievements

In this study, we aimed to elucidate the neural basis of "exploratory navigation" based on uncertain location information in a model animal, the nematode C. elegans. The results of this study include "elucidation of the molecular mechanism of decision making by differentiation and integration," "development of AI techniques to estimate internal states from behavioral trajectories," and "development of AI techniques to efficiently measure whole-brain neural activity in C. elegans," and some of the results were developed into international collaborative research.

Academic Significance and Societal Importance of the Research Achievements

主な成果の１つである「行動軌跡から内部状態を推定する人工知能技術」は、線虫だけでなくペンギンや海鳥などさまざまな動物の軌跡から、記憶や感情を反映する内部状態を推定する画期的な技術であり、Nature系のWebメディアから取材も受けた。また、もう１つの主要な成果である「全脳神経活動計測を効率的に行うための人工知能技術」は、線虫だけでなく小型魚類の心筋細胞やガン細胞の活動解析などにも応用することができ、この技術も大きな注目を浴びた。このように、本研究によって、線虫の脳活動のメカニズムを解明するのみならず幅広い生命科学分野に貢献できる人工知能技術を開発することができた。

Research Products

• [Int'l Joint Research] コロンビア大学(米国)
• [Int'l Joint Research] コロンビア大学(米国)
• [Int'l Joint Research] The University of Edinburgh(英国)
• [Journal Article] Calcium Imaging of Neuronal Activity under Gradually Changing Odor Stimulation in Caenorhabditis elegans (2021)
  • Author(s): Tanimoto Yuki、Kimura Koutarou
  • Journal Title: BIO-PROTOCOL Volume: 11 Issue: 1
  • DOI: 10.21769/bioprotoc.3866
  • Peer Reviewed / Open Access
• [Journal Article] 3DeeCellTracker, a deep learning-based pipeline for segmenting and tracking cells in 3D time lapse images (2021)
  • Author(s): Wen Chentao、Miura Takuya、Voleti Venkatakaushik、Yamaguchi Kazushi、Tsutsumi Motosuke、Yamamoto Kei、Otomo Kohei、Fujie Yukako、Teramoto Takayuki、Ishihara Takeshi、Aoki Kazuhiro、Nemoto Tomomi、Hillman Elizabeth MC、Kimura Koutarou D
  • Journal Title: eLife Volume: 10
  • DOI: 10.7554/elife.59187
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cross-species behavior analysis with attention-based domain-adversarial deep neural networks (2021)
  • Author(s): Maekawa Takuya、Higashide Daiki、Hara Takahiro、Matsumura Kentarou、Ide Kaoru、Miyatake Takahisa、Kimura Koutarou D.、Takahashi Susumu
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 5519-5519
  • DOI: 10.1038/s41467-021-25636-x
  • Peer Reviewed / Open Access
• [Journal Article] クローズアップ実験法 series 338 三次元自動細胞追跡ツール:3DeeCellTrackerで解析できることと使い方 (2021)
  • Author(s): Wen Chentao, 木村幸太郎
  • Journal Title: 実験医学 Volume: 39 Pages: 2264-2272
• [Journal Article] Deep learning-assisted comparative analysis of animal trajectories with DeepHL (2020)
  • Author(s): Takuya Maekawa, Kazuya Ohara, Yizhe Zhang, Matasaburo Fukutomi, Sakiko Matsumoto, Kentarou Matsumura, Hisashi Shidara, Shuhei J. Yamazaki, Ryusuke Fujisawa, Kaoru Ide, Naohisa Nagaya, Koji Yamazaki, Shinsuke Koike, Takahisa Miyatake, Koutarou D. Kimura, Hiroto Ogawa, Susumu Takahashi, and Ken Yoda
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 5316-5316
  • DOI: 10.1038/s41467-020-19105-0
  • Peer Reviewed / Open Access
• [Journal Article] 機械学習による移動行動解析の考え方 (2020)
  • Author(s): 木村幸太郎
  • Journal Title: 実験医学増刊「機械学習を生命科学に使う！」 Volume: 38 Pages: 3501-3507
• [Journal Article] How do we know how the brain works??Analyzing whole brain activities with classic mathematical and machine learning methods (2020)
  • Author(s): Wen Chentao、Kimura Koutarou D.
  • Journal Title: Japanese Journal of Applied Physics Volume: 59 Issue: 3 Pages: 030501-030501
  • DOI: 10.35848/1347-4065/ab77f3
  • Peer Reviewed / Open Access
• [Journal Article] Neuron ID dataset facilitates neuronal annotation for whole-brain activity imaging of C. elegans (2020)
  • Author(s): Yu Toyoshima, Stephen Wu, Manami Kanamori, Hirofumi Sato, Moon Sun Jang, Suzu Oe, Yuko Murakami, Takayuki Teramoto, Chanhyun Park, Yuishi Iwasaki, Takeshi Ishihara, Ryo Yoshida & Yuichi Iino
  • Journal Title: BMC Biology Volume: 18 Issue: 1 Pages: 30-30
  • DOI: 10.1186/s12915-020-0745-2
  • Peer Reviewed / Open Access
• [Journal Article] STEFTR: A Hybrid Versatile Method for State Estimation and Feature Extraction From the Trajectory of Animal Behavior. (2019)
  • Author(s): Yamazaki SJ,Ohara K,Ito K,Kokubun N,Kitanishi T,Takaichi D,Yamada Y,Ikejiri Y,Hiramatsu F,Fujita K,Tanimoto Y,Yamazoe-Umemoto A,Hashimoto K,Sato K,Yoda K,Takahashi A,Ishikawa Y,Kamikouchi A,Hiryu S,Maekawa T,Kimura KD
  • Journal Title: Frontiers in neuroscience Volume: 13 Pages: 626-626
  • DOI: 10.3389/fnins.2019.00626
  • Peer Reviewed / Open Access
• [Journal Article] Real-time volumetric microscopy of in vivo dynamics and large-scale samples with SCAPE 2.0 (2019)
  • Author(s): Voleti Venkatakaushik、Patel Kripa B.、Li Wenze、Perez Campos Citlali、Bharadwaj Srinidhi、Yu Hang、Ford Caitlin、Casper Malte J.、Yan Richard Wenwei、Liang Wenxuan、Wen Chentao、Kimura Koutarou D.、Targoff Kimara L.、Hillman Elizabeth M. C.
  • Journal Title: Nature Methods Volume: 16 Issue: 10 Pages: 1054-1062
  • DOI: 10.1038/s41592-019-0579-4
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Efficient Learning Algorithm for Sparse SubSequence Pattern-based Classication and Applications to Comparative Animal Trajectory Data Analysis (2019)
  • Author(s): Takuto Sakuma, Kazuya Nishi, Kaoru Kishimoto, Kazuya Nakagawa, Masayuki Karasuyama, Yuta Umezu, Shinsuke Kajioka, Shuhei J. Yamazaki, Koutarou D. Kimura, Sakiko Matsumoto, Ken Yoda, Matasaburo Fukutomi, Hisashi Shidara, Hiroto Ogawa, Ichiro Takeuchi
  • Journal Title: Advanced Robotics Volume: 33 Issue: 3-4 Pages: 134-152
  • DOI: 10.1080/01691864.2019.1571438
  • Peer Reviewed / Open Access
• [Journal Article] Neuronal, mathematical, and molecular bases of perceptual decision-making in C. elegans (2019)
  • Author(s): Tanimoto Yuki、Kimura Koutarou D.
  • Journal Title: Neuroscience Research Volume: 140 Pages: 3-13
  • DOI: 10.1016/j.neures.2018.10.010
  • Peer Reviewed
• [Journal Article] Measuring Spatiotemporal Dynamics of Odor Gradient for Small Animals by Gas Chromatography (2018)
  • Author(s): Yamazoe-Umemoto Akiko、Iwasaki Yuishi、Kimura Koutarou D.
  • Journal Title: BIO-PROTOCOL Volume: 8 Issue: 7 Pages: 2797-2797
  • DOI: 10.21769/bioprotoc.2797
  • Peer Reviewed / Open Access
• [Journal Article] Temporal Differentiation and Integration of Sensory Information for Decision-making of <i>C. elegans</i> (2018)
  • Author(s): 谷本 悠生、木村 幸太郎
  • Journal Title: Seibutsu Butsuri Volume: 58 Issue: 2 Pages: 083-085
  • DOI: 10.2142/biophys.58.083
  • NAID: 130006594327
  • ISSN: 0582-4052, 1347-4219
  • Peer Reviewed
• [Journal Article] Neural mechanisms of animal navigation. (2018)
  • Author(s): Kimura KD, Sato M, Sakura M
  • Journal Title: Proceedings os 6th International Conference DAPI Volume: 印刷中 Pages: 65-81
  • DOI: 10.1007/978-3-319-91131-1_5
  • ISBN: 9783319911304, 9783319911311
  • Peer Reviewed / Open Access
• [Journal Article] 生物のナビゲーションに学ぶ(第4回)動物ナビゲーションの神経基盤 (2018)
  • Author(s): 木村 幸太郎, 佐藤 正晃, 佐倉 緑
  • Journal Title: 遺伝 : 生物の科学 Volume: 72 Pages: 512-518
  • NAID: 40021664321
• [Journal Article] Calcium dynamics regulating the timing of decision-making in C. elegans (2017)
  • Author(s): Tanimoto Yuki、Yamazoe-Umemoto Akiko、Fujita Kosuke、Kawazoe Yuya、Miyanishi Yosuke、Yamazaki Shuhei J、Fei Xianfeng、Busch Karl Emanuel、Gengyo-Ando Keiko、Nakai Junichi、Iino Yuichi、Iwasaki Yuishi、Hashimoto Koichi、Kimura Koutarou D
  • Journal Title: eLife Volume: 6
  • DOI: 10.7554/elife.21629
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 匂い濃度の微分と積分による線虫ナビゲーションにおける意思決定 (2017)
  • Author(s): 木村幸太郎、谷本悠生
  • Journal Title: アロマリサーチ Volume: 18 Pages: 266-271
• [Journal Article] 匂いナビゲーションのための線虫の「意思決定」とその情報演算 (2017)
  • Author(s): 谷本悠生、木村幸太郎
  • Journal Title: 生物の科学 遺伝 Volume: 71 Pages: 512-518
• [Journal Article] ロボット顕微鏡が解析する線虫の行動とドーパミンの関係 (2016)
  • Author(s): 木村 幸太郎, 谷本悠生
  • Journal Title: 日本ロボット学会誌 Volume: 34 Pages: 609-613
  • NAID: 130005250301
• [Journal Article] ロボット顕微鏡システムによる神経細胞活動計測と操作 (特集 光×ロボット) (2016)
  • Author(s): 谷本悠生, 木村幸太郎
  • Journal Title: Optronics Volume: 35 Pages: 69-74
• [Presentation] 3DeeCellTracker: a deep learning-based method for tracking cells in 3D time lapse images (2021)
  • Author(s): Wen C, Kimura K
  • Organizer: The 15th IEEE International Conference on Nano/Molecular Medicine & Engineering (IEEE-NANOMED 2021)
  • Int'l Joint Research / Invited
• [Presentation] 微分・積分フィルタによる線虫の意思決定 (2019)
  • Author(s): 木村幸太郎
  • Organizer: RIMS共同研究「自己組織化による適応フィルタの創発性について」
  • Invited
• [Presentation] シンプルな神経系における『演算』と『因果律』 (2019)
  • Author(s): 木村幸太郎
  • Organizer: 応用物理学会秋季学術講演会
  • Invited
• [Presentation] Data-driven predictive models for information processing in the small brain of Caenorhabditis elegans. (2019)
  • Author(s): Wen C, Kimura K.
  • Organizer: 28th Annual Computational Neuroscience Meeting.
  • Int'l Joint Research
• [Presentation] Analyzing whole brain activities of a worm using data-driven models. (2019)
  • Author(s): Wen C, Kimura K.
  • Organizer: 11th Asian Conference on Machine Learning.
  • Int'l Joint Research
• [Presentation] Data-driven predictive models for information processing in the (small) brain. (2019)
  • Author(s): Wen C, Kimura K
  • Organizer: Neuro2019（第42回日本神経科学大会 第62回日本神経化学会大会）
  • Invited
• [Presentation] A hybrid versatile method for state estimation and feature extraction from the trajectory of animal behavior. (2019)
  • Author(s): Kimura K, Yamazaki SJ, Kitanishi T, Yoda K, Takahashi A, Kamikouchi A, Hiryu S, Maekawa T.
  • Organizer: Neuro2019（第42回日本神経科学大会 第62回日本神経化学会大会）
• [Presentation] Robotic Microscope System for Studying the basic principles of brain function (2018)
  • Author(s): Kimura, K.D., Hashimoto, K.
  • Organizer: International Symposium on Mcro-Nano Mechatronics and Human Science.
  • Int'l Joint Research / Invited
• [Presentation] Learning-dependent neural gain control by asymmetric modulation of first- and second-order time-differential of stimulus in sensory neurons. (2018)
  • Author(s): Yosuke Ikejiri, Yuki Tanimoto, Shuhei J. Yamazaki, Kosuke Fujita, Kotaro Kimura.
  • Organizer: C. elegans topic meeting: neuronal development, synaptic function & behavior.
  • Int'l Joint Research
• [Presentation] A flexible pipeline for 3D whole brain imaging with deep learning. (2018)
  • Author(s): Wen C, Miura T, Fujie Y, Teramoto T, Ishihara T, Kimura K.
  • Organizer: C. elegans topic meeting: neuronal development, synaptic function & behavior.
  • Int'l Joint Research
• [Presentation] A unified method to analyze the behavioral states and features during animal’s navigation by machine learning. (2018)
  • Author(s): Yamazaki S , Yoda K , Maekawa T , Kimura K.
  • Organizer: C. elegans topic meeting: neuronal development, synaptic function & behavior.
  • Int'l Joint Research
• [Presentation] Trajectory analysis of navigation by machine learning: experience-dependent modulation of olfactory behavior in C. elegans. (2018)
  • Author(s): Kimura K, Yamazaki S, Ikejiri Y, Maekawa T.
  • Organizer: 第41回日本神経科学大会
• [Presentation] Differential equations for decision-making in worm’s navigation (2017)
  • Author(s): Kimura Kotaro
  • Organizer: Tutorial Workshops on Systems Science on Bio-navigation, IEEE ICMA 2017 Conference.
  • Int'l Joint Research / Invited
• [Presentation] Calcium dynamics regulating the timing of decision-making in C. elegans (2017)
  • Author(s): Kimura Kotaro
  • Organizer: The Optical Revolution in Physiology: From Membrane to Brain, Society of General Physiologists 71st Annual Symposium.
  • Int'l Joint Research
• [Presentation] 意思決定のための線虫の感覚情報演算メカニズム (2017)
  • Author(s): 木村幸太郎
  • Organizer: 生理学研究所情動研究会「先天的と後天的なメカニズム融合による情動・行動の理解と制御」
  • Invited
• [Presentation] 複数の神経回路メカニズムによって制御される線虫C. elegansの非連合匂い学習 (2017)
  • Author(s): 木村幸太郎、山崎修平
  • Organizer: 2017年度生命科学系学会合同年次大会
  • Invited
• [Presentation] Towards identifying neuropeptide signaling that regulates repulsive odor learning. (2016)
  • Author(s): Yamaguchi A, Yamazoe A, Yamazaki S, Fujita K and Kimura K.
  • Organizer: C. elegans topic meeting: neuronal development, synaptic function & behavior.
  • Int'l Joint Research
• [Presentation] A metabotropic glutamate receptor MGL-2 regulates repulsive olfactory learning. (2016)
  • Author(s): Yamazaki S, Ishihara T, Kimura K.
  • Organizer: C. elegans topic meeting: neuronal development, synaptic function & behavior.
  • Int'l Joint Research
• [Presentation] In actio optophysiological analyses reveal functional diversification of dopaminergic neurons in the nematode C. elegans. (2016)
  • Author(s): Tanimoto Y, Zheng YG, Fei X, Fujie Y, Hashimoto K, Kimura K.
  • Organizer: C. elegans topic meeting: neuronal development, synaptic function & behavior.
  • Int'l Joint Research
• [Presentation] A metabotropic glutamate receptor regulates olfactory learning in a pair of multisensory integrating neurons in C. elegans. (2016)
  • Author(s): Yamazaki S, Ikejiri Y, Tanimoto Y, Ishihara T, Kimura K.
  • Organizer: 第39回日本神経科学大会
• [Presentation] In actio optophysiological analyses reveal functional diversification of dopaminergic neurons in the nematode C. elegans. (2016)
  • Author(s): Tanimoto Y, Zheng YG, Fei X, Fujie Y, Hashimoto K, Kimura K.
  • Organizer: 第39回日本神経科学大会
• [Book] From Connectome to Function: Using Optogenetics to Shed Light on the Caenorhabditis elegans Nervous system. In Optogenetics: From Neuronal Function to Mapping and Disease Biology (2017)
  • Author(s): Kimura, K.D., Busch, K.E.
  • Total Pages: 502
  • Publisher: Cambridge University Press
  • ISBN: 9781107053014
• [Remarks] 木村研究室HP
  • URL: https://www.kokimura-lab.org