Human infants acquire cognitive capabilities in their first few years of life. Although the behavioral dynamics of this developmental process has been closely analyzed, the underlying mechanisms remain a mystery. We aim to understand the neural basis of cognitive development by means of computational approaches based on a theoretical framework called predictive coding. In this theory, the brain tries to minimize prediction errors by updating its internal models or altering the environment by active inference. We design computational neural networks based on predictive coding and implement them in robots to investigate how the theory may explain the continuity and diversity of cognitive development. Inspired by these computational studies, we also design assistive systems for developmental disorders such as autism spectrum disorder (ASD). Through this research individuals with ASD would understand better themselves and thereby enhance social activities by making their cognitive process observable.
Nagai, Y.: Predictive Learning: Its key role in early cognitive development. Philosophical Transactions of the Royal Society B, in press.
Horii, T., Nagai, Y., and Asada, M.: Modeling Development of Multimodal Emotion Perception Guided by Tactile Dominance and Perceptual Improvement. IEEE Transactions on Cognitive and Developmental Systems, 10(3):762-775, 2018.
Baraglia, J., Nagai, Y., and Asada, M.: Emergence of Altruistic Behavior Through the Minimization of Prediction Error. IEEE Transactions on Cognitive and Developmental Systems, 8(3):141-151, 2016.
Ugur, E., Nagai, Y., Sahin, E., and Oztop, E.: Staged Development of Robot Skills: Behavior Formation, Affordance Learning and Imitation with Motionese. IEEE Transactions on Autonomous Mental Development, 7(2):119-139, 2015.
Nagai, Y. and Rohlfing, K. J.: Computational Analysis of Motionese Toward Scaffolding Robot Action Learning. IEEE Transactions on Autonomous Mental Development, 1(1):44-54, 2009.
Nagai, Y., Hosoda, K., Morita, A., and Asada, M.: A constructive model for the development of joint attention. Connection Science, 15(4):211-229, 2003.
I received a B.E. and M.E. from Aoyama Gakuin University in 1997 and 1999, respectively, and then completed a Ph.D. in Engineering at Osaka University in 2004. After working at the National Institute of Information and Communications Technology (NICT) and at Bielefeld University for five years, I became a Specially Appointed Associate Professor at Osaka University in 2009 and a Senior Researcher at NICT in 2017, where I gained experience in both international and interdisciplinary research. From 2016, I have served as Project Leader of the JST CREST Program in Cognitive Mirroring. I joined IRCN at The University of Tokyo in April 2019 to continue my research on the neural mechanisms of human cognitive development via computational and robotic technologies.
How do human infants acquire their native language with such astonishing speed and efficiency? Our laboratory examines the role of the social environment in rapid language acquisition. Using behavioral and brain imaging techniques, we seek to discover and define mechanisms through which social factors and environments influence the early acquisition of speech sounds and words. What is the role of different social cues during the learning process? How does learning change as a function of an infant’s age and environment? In answering these questions, our goal is to develop useful theoretical frameworks and practical tools to measure and improve language learning in infants.
Tsuji, S., Mazuka, R., & Swingley, D. (2019) Temporal contingency augments attention to a referent in a word learning task. To be published in: Proceedings of the 43rd annual Boston University Conference on Language Development.
Bergmann, C., Tsuji, S., Piccinini, P.E., Lewis, M.L., Braginsky, M., Frank, M.C., & Cristia, A. (2018). Promoting replicability in developmental research through meta-analyses: Insights from language acquisition research. Child Development, 89, 1996-2009. doi:10.1111/cdev.13079
Tsuji, S., Fikkert, P., Minagawa, Y., Dupoux, E., Filippin, L., Versteegh, M., Hagoort, P., & Cristia, A. (2017). The more, the better? Behavioral and neural correlates of frequent and infrequent vowel exposure. Developmental Psychobiology, 59(5), 603-612. doi: 10.1002/dev.21534.
Tsuji, S., Mazuka, R., Cristia, A., & Fikkert, P. (2015). Even at 4 months, a labial is a good enough coronal, but not vice versa. Cognition, 134, 252-256. doi:10.1016/j.cognition.2014.10.009.
After undergraduate studies in Psychology at Humboldt University in Berlin, I became fascinated with infant language development during a research stint in the Laboratory for Language Development at the RIKEN Brain Science Institute. I earned a Ph.D. from the International Max Planck Research School for Language Sciences at Radboud University and the Max Planck Institute for Psycholinguistics, followed by postdoctoral research at the Infant Language Center at the University of Pennsylvania and Laboratory of Cognitive Sciences and Psycholinguistics at Ecole Normale Supérieure.
Functional magnetic resonance neuroimaging (fMRI) facilitates the quantitative assessment of brain structure and function in vivo. Our laboratory conducts human brain MRI studies in healthy human adolescent development and patients with psychiatric diseases to understand the mechanisms linking them. Recently, we have reported alterations of subcortical regional volumes in patients with schizophrenia using a large-scale data set from a multi-site consortium. Current research is directed to elucidate psychiatric disorders by revealing their neurobiological substrates and developing biomarkers for clinical applications. In addition, given the importance for MRI researchers to collaborate internationally, to connect human and animal research, and to apply machine learning and artificial intelligence techniques, we collaborate extensively with multi-disciplinary researchers.
Okada N, Ando S, Sanada M, Hirata-Mogi S, Iijima Y, Sugiyama H, Shirakawa T, Yamagishi M, Kanehara A, Morita M, Yagi T, Hayashi N, Koshiyama D, Morita K, Sawada K, Ikegame T, Sugimoto N, Toriyama R, Masaoka M, Fujikawa S, Kanata S, Tada M, Kirihara K, Yahata N, Araki T, Jinde S, Kano Y, Koike S, Endo K, Yamasaki S, Nishida A, Hiraiwa-Hasegawa M, Bundo M, Iwamoto K, Tanaka SC, Kasai K. The population-neuroscience study of the Tokyo TEEN Cohort (pn-TTC): a cohort longitudinal study to explore the neurobiological substrates of adolescent psychological and behavioral development. Psychiatry Clin Neurosci [Epub ahead of print]
Okada N, Yahata N, Koshiyama D, Morita K, Sawada K, Kanata S, Fujikawa S, Sugimoto N, Toriyama R, Masaoka M, Koike S, Araki T, Kano Y, Endo K, Yamasaki S, Ando S, Nishida A, Hiraiwa-Hasegawa M, Edden RAE, Barker PB, Sawa A, Kasai K. Neurometabolic and functional connectivity basis of prosocial behavior in early adolescence. Sci Rep 2019;9:732.
Okada N, Yahata N, Koshiyama D, Morita K, Sawada K, Kanata S, Fujikawa S, Sugimoto N, Toriyama R, Masaoka M, Koike S, Araki T, Kano Y, Endo K, Yamasaki S, Ando S, Nishida A, Hiraiwa-Hasegawa M, Kasai K. Abnormal asymmetries in subcortical brain volume in early adolescents with subclinical psychotic experiences. Transl Psychiatry 2018;8:254.
Okada N, Fukunaga M, Yamashita F, Koshiyama D, Yamamori H, Ohi K, Yasuda Y, Fujimoto M, Watanabe Y, Yahata N, Nemoto K, Hibar D, van Erp T, Fujino H, Isobe M, Isomura S, Natsubori N, Narita H, Hashimoto N, Miyata J, Koike S, Takahashi T, Yamasue H, Matsuo K, Onitsuka T, Iidaka T, Kawasaki Y, Yoshimura R, Watanabe Y, Suzuki M, Turner J, Takeda M, Thompson P, Ozaki N, Kasai K, Hashimoto R; COCORO: Abnormal asymmetries in subcortical brain volume in schizophrenia. Mol Psychiatry 2016;21:1467-1476.
Okada N, Takahashi K, Nishimura Y, Koike S, Ishii-Takahashi A, Sakakibara E, Satomura Y, Kinoshita A, Takizawa R, Kawasaki S, Nakakita M, Ohtani T, Okazaki Y, Kasai K: Characterizing prefrontal cortical activity during inhibition task in methamphetamine-associated psychosis versus schizophrenia: A multi-channel near-infrared spectroscopy study. Addict Biol 2016;21:489-503.
I obtained an M.D. degree from the Faculty of Medicine of the University of Tokyo in 2004. After a junior residency, I started psychiatry training at the University of Tokyo Hospital in 2006 and then worked as a psychiatrist at Tokyo Metropolitan Matsuzawa Hospital from 2007 to 2012. I became an Assistant Professor at the University of Tokyo Hospital in 2012 and concurrently entered the Graduate School of Medicine of the University of Tokyo earning a Ph.D. degree in 2017, before joining IRCN in 2019 where I manage the human fMRI scanner facility. At the same time, I am continuing research on the neuroimaging of psychiatric disorders and adolescent development.
The predictive coding theory proposes that the brain continuously generates and updates predictions of sensory information at multiple levels of abstraction, and emits prediction-error signals when the predicted and actual sensory inputs differ. This framework offers a unified model of perception and action, and may offer insight into psychiatric disorders where prediction or error signals may go awry, such as schizophrenia and autism. My current research interests focus on: (1) grounding the theory by identifying brain signals that subserve predictions and prediction errors at different hierarchical levels, and (2) generalizing the theory into cognitive domains other than perception and action. A better understanding of how information at different spatial and temporal scales merges into coherent unity can facilitate the development of neuromorphic engineering and advance the search for neural markers for the prognosis and diagnosis of brain disorders.
Chao ZC, Takaura K, Wang L, Fujii N, Dehaene S (2018). Large-scale cortical networks for hierarchical prediction and prediction error in the primate brain. Neuron, 100, 1252-1266
Chao ZC, Sawada M, Isa T, Nishimura Y (2018). Dynamic Reorganization of Motor Networks During Recovery from Partial Spinal Cord Injury in Monkeys. Cerebral Cortex, bhy172.
Chao ZC, Nagasaka Y, Fujii N (2015). Cortical network architecture for context processing in primate brain.” eLife 4: e06121.
Fukushima M, Chao ZC, Fujii N (2015). Studying cortical circuits with electrocorticography in non-human primates: recent advances. Current Opinion in Neurobiology, 32, 124-131.
Chao ZC, Fujii N (2013). Mining spatio-spectro-temporal cortical dynamics: a guideline for offline and online electrocorticographic analyses. in Advanced Methods in Neuroethological Research, Hiroto Ogawa and Kotaro Oka, editors, Springer, 39-55.
Chao ZC, Nagasaka Y, Fujii N (2010). Long-term asynchronous decoding of arm motion using electrocorticographic signals in monkeys. Frontiers in Neuroengineering 3:3. doi:10.3389/fneng.2010.00003.
Zenas Chao is fascinated by the human mind and the development of machines with human-like intelligence, and curious about the biological origins of free will, and consciousness. After graduating from college in Taiwan with a dual B.S. in Life Science and Chemistry, he attended Georgia Institute of Technology in the United States to study Biomedical Engineering. For his Ph.D., he grew neurons in petri dishes and connected them to robots demonstrating that a machine with an artificial organic brain can learn purposeful behavior. After graduation, he moved to Japan and held positions at the RIKEN Brain Science Institute as a Research Scientist, the National Institute for Physiological Sciences as an Assistant Professor, and Kyoto University as a Junior Associate Professor, to study how to decode brain signals from behaving humans and monkeys and enable the control of robots and computers by the brain. In September 2019 he joined the International Research Center for Neurointelligence (IRCN) at the University of Tokyo as a Project Associate Professor, using his research experience in silico, in vitro, and in vivo, to search for evidence of predictive coding, a framework that many consider a “grand unified theory of cognition”.
Neuroscience is a research area at the intersection of many diverse fields. The prospects of neuroscience have the potential to improve society, and awareness of the human brain as one of Earth’s key resources and the new technologies to study it has captured public imagination. But neuroscience is also burdened with inefficient, aging research systems governing lab structure and collaboration, career development, publishing, education, funding, and public outreach. My current work considers neuroscience as an ecosystem in need of rebuilding with elemental principles and programs for effective, sustainable coordination across the community. Starting from the construction of research projects and papers, funding and collaboration, and science communication, I pursue projects that re-envision the scientific ecosystem and build a foundation for the future of science.
Moskowitz, H.S., Yokoyama, C.T. and Ryan, T.A. (2005) Highly Cooperative Control of Endocytosis by Clathrin. Mol Biol Cell 16:1769-76.
Yokoyama, C.T., Myers, S.J., Fu, J., Mockus, S.M., Scheuer, T. and Catterall, W.A. (2005) Mechanism of SNARE Protein Binding and Regulation of CaV2.2 Channels by Phosphorylation of the Synaptic Protein Interaction Site. Mol Cell Neurosci 28:1-17.
Mochida, S., Westenbroek, R.E., Yokoyama, C.T., Zhong, H., Myers, S.J., Scheuer, T., Itoh, K. and Catterall, W.A. (2003) Requirement for the Synaptic Protein Interaction Site for Reconstitution of Synaptic Transmission in Sympathetic Ganglion Neurons by P/Q-type Calcium Channels. Proc Natl Acad Sci USA 100:2819-2824.
Zhong, H., Yokoyama, C.T., Scheuer, T. and Catterall, W.A. (1999) Reciprocal Regulation of P/Q-type Ca2+ channels by SNAP-25, Syntaxin, and Synaptotagmin. Nature Neurosci 2:939- 941.
Yokoyama, C.T., Sheng, Z.-H. and Catterall, W.A. (1997) Phosphorylation of the Synaptic Protein Interaction Site on N-type Calcium Channels Inhibits Interactions with SNARE Proteins. J Neurosci 17:6929- 6938.
Yokoyama, C.T., Westenbroek, R.E., Hell, J.W., Soong, T.W., Snutch, T.P. and Catterall, W.A. (1995) Biochemical Properties and Subcellular Distribution of the Neuronal Class E Calcium Channel á1 Subunit. J Neurosci 15:6419-6432.
I was a postdoctoral researcher at Weill-Cornell Medical School after earning a Ph.D. from the University of Washington-Seattle in neurobiology, M.S. from the Massachusetts Institute of Technology in biology and B.S. from Michigan State University in biochemistry. I studied the function and regulation of voltage-gated ionic channels and their associated proteins in presynaptic nerve terminals. In a second career phase, I served as a senior scientific editor for the journal Neuron, managing peer review of research manuscripts and review articles. In my current position, I am a research administrator with emphases on executive management, scientific communication support and training, and the design of novel research ecosystems for sustainable transdisciplinary collaboration and team science.
IRCN Director / Principal Investigator / Project Professor
Professor of Neurology, Harvard Medical School, Boston Children’s Hospital
Professor of Molecular & Cellular Biology, Center for Brain Science, Harvard University
Critical Periods in Brain Development and their Clinical Applications
Early life experience shapes brain function – from motor skills to language and emotions. We explore the biological basis of these windows of opportunity and vulnerability and how they are derailed in mental illness. Integrating molecular, cellular and systems neuroscience, our work has revealed these “critical periods” are themselves plastic and reversible. Specific, inhibitory (GABA) circuits trigger their onset timing, while “brake”-like factors actively prevent circuit rewiring when they close. Translational research inspired by this work targets recovery from neurodevelopmental disorders, such as amblyopia, epilepsy and autism spectrum disorders, as well as the potential for recovery of function later in life.
Takesian AE, Bogart LJ, Lichtman JW, Hensch TK. (2018) Inhibitory circuit gating of auditory critical-period plasticity. Nature Neurosci. 21:218-227
Kobayashi Y, Ye Z, Hensch TK. (2015) Clock genes control cortical critical period timing. Neuron. 86:264-75.
Werker JF, Hensch TK. (2015) Critical periods in speech perception: new directions. Annu Rev Psychol. 66:173-96. Gogolla, N., Takesian, A.E., Feng, G., Fagiolini, M. & Hensch, T.K. (2014) Sensory integration in mouse insular cortex reflects GABA circuit maturation. Neuron 83: 894-905.
Barkat, T.R., Polley, D.B. & Hensch, T.K. (2011) A critical period for auditory thalamocortical connectivity. Nature Neurosci. 14:1189-1194.
Morishita, H., Miwa, J.M., Heintz, N. & Hensch, T.K. (2010) Lynx1, a cholinergic brake, limits plasticity in adult visual cortex. Science 330:1238-1240.
Yazaki-Sugiyama, Y., Kang, S., Cateau, H., Fukai, T. & Hensch, T.K. (2009) Bidirectional plasticity in fast-spiking GABA circuits by visual experience. Nature 462: 218-21.
Sugiyama, S., Di Nardo, A., Aizawa, S., Matsuo, I., Volovitch, M., Prochiantz, A. & Hensch, T.K. (2008) Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity. Cell 134: 508-520.
Hensch, T.K. (2005) Critical period plasticity in local cortical circuits. Nature Reviews Neurosci. 6: 877-888. Fagiolini, M., Fritschy, J-M., Löw, K., Möhler, H., Rudolph, U. & Hensch, T.K. (2004) Specific GABAA circuits for visual cortical plasticity. Science 303: 1681-1683.
Hensch, T.K & Stryker, M.P. (2004) Columnar architecture sculpted by GABA circuits in developing cat visual cortex. Science 303: 1678-1681. Fagiolini, M. & Hensch, T.K. (2000) Inhibitory threshold for critical-period activation in primary visual cortex. Nature 404: 183-186.
Hensch, T.K., Fagiolini, M., Mataga, N., Stryker, M.P., Baekkeskov, S. & Kash, S.F. (1998) Local GABA circuit control of experience-dependent plasticity in the developing visual cortex. Science 282:1504-1508.
After training with Drs J Allan Hobson at Harvard (AB), Masao Ito at UTokyo (MPH), Wolf Singer at the Max-Planck Institute for Brain Research (Fulbright fellow), and Michael P Stryker at the University of California San Francisco (PhD Neuroscience, 1996), Hensch helped to launch the RIKEN Brain Science Institute, initially as Lab Head for Neuronal Circuit Development then Group Director for Critical Period Mechanisms Research. He returned to Harvard in 2006 as joint Professor of Neurology and Molecular Cellular Biology, where he directs the NIMH Silvio Conte Center for Mental Health Research. Career honors include the Society for Neuroscience Young Investigator Award both in Japan (Tsukahara Prize, 2001) and the US (2005), the NIH Director's Pioneer Award (2007), Sackler Prize (2016) and co-Director of the CIFAR Child Brain Development network (2019). Hensch also serves on the editorial board of several prominent journals, including Neuron, Neural Development and Frontiers in Neural Circuits (Chief Editors).
Neuroscience is an interdisciplinary research field that is linked by a wide variety of research fields. Theoretical approaches to neuroscience have helped to introduce new ideas and shape directions of neuroscience research. In modern neuroscience, theoretical neuroscience is assuming an increasingly important role due to big data obtained by experimental measurement and the recent development of artificial intelligence. In my current work, I focus on theories of neuronal data analysis and neural network modeling with the aim of bridging the gap between experimental and theoretical neuroscience studies.
Ohnishi H, Shimada Y, Fujiwara K, Ikeguchi T. Chaotic neurodynamical search with small number of neurons for solving QAP, Nonlinear Theory and Its Applications, IEICE, Vol. 8, No. 3, pp. 255-265, 2017.
Kobayashi T, Shimada Y, Fujiwara K, Ikeguchi T. Reproducing infra-slow oscillations with dopaminergic modulation, Scientific Reports, 7: 2411, 2017.
Fujiwara K, Suzuki H, Ikeguchi T, Aihara K. Method for analyzing time-varying statistics on point process data with multiple trials, Nonlinear Theory and its Applications, IEICE, Vol. 6, No. 1, 2015.
Kuroda K, Hashiguchi H, Fujiwara K, Ikeguchi T. Reconstruction of network structures from marked point processes using multi-dimensional scaling, Physica A, Vol.415, pp.194-204, 2014.
Kurebayashi W, Fujiwara K, Ikeguchi T. Colored noise induces synchronization of limit cycle oscillators, EPL (Europhysics Letters), Vol.97, p.50009, 2012.
Kantaro Fujiwara and Kazuyuki Aihara. Time-varying irregularities in multiple trial spike data, European Physical Journal B, Vol. 68, pp. 283-289, 2009.
Fujiwara K, Aihara K. Trial-to-trial Variability and its influence on higher order statistics, Journal of Artificial Life and Robotics, Vol. 13, pp. 470-473, 2009.
Fujiwara K, Fujiwara H, Tsukada M, Aihara K. Reproducing bursting interspike interval statistics of the gustatory cortex, Biosystems, Vol. 90, pp. 442-448, 2007.
I received a Ph. D. in Information Science and Technology from the University of Tokyo. I studied computational neuroscience, especially the mathematical modeling of single neurons, and neural network modeling of learning and adaptation. As a postdoctoral researcher for JSPS, I studied data analysis of neural systems, including a theory for neural spike train analysis. As an Assistant Professor at Saitama University and Tokyo University of Science, I studied nonlinear mathematics and its applications. Current, I am aiming to bridge the gap between experimental and theoretical neuroscience. I also manage the data science core servers and software for the IRCN community.
We act based on sensory information from the outside world, perceived by peripheral sensory organs and sent to a specific part of the cerebral cortex depending on the type of sensation. In the cortex, neurons extract specific external features, but its mechanism is largely unknown. My laboratory is focused on vision and the principles of visual information processing in cortical neurons. We conduct researches at two levels: single cells and networks. We image the activities of soma, axons and spines using two-photon microscopy, optogenetics and anatomical tracing in mouse as an animal model. Our goal is to clarify the information processing rules embedded in single cortical neurons and neuronal circuit, and contributing to potential working principles for artificial intelligence.
Kondo S, Yoshida T, Ohki K (2016) Mixed functional microarchitectures for orientation selectivity in the mouse primary visual cortex. Nature Communications 7:13210.
Kondo S, Ohki K (2016) Laminar differences in the orientation selectivity of geniculate afferents in mouse primary visual cortex. Nature Neuroscience 19:316-319.
Kubota, Y, Kondo, S, Nomura, M, Hatada, S, Yamaguchi, N, Mohamed, A A, Karube, F, Luebke, J, Kawaguchi, Y (2015) Functional effects of distinct innervation styles of pyramidal cells by fast spiking cortical interneurons. eLIFE e07919.
Kondo S, Okabe S (2013) Two-photon microscopy analysis of cell dynamics of microglia. Molecular Biology of Cells: Microglia; Methods and Protocols. Edited by Joseph B and Venero JL. Humana Press, New York, 319-335.
Kondo S, Kohsaka S, Okabe S (2011) Long-term changes of spine dynamics and microglia after transient peripheral immune response triggered by LPS in vivo. Mol. Brain 4: 27.
I earned a Ph.D. from The University of Tokyo in Cellular Neurobiology (Prof. Hirokawa’s Lab), M.S. from the Tokyo Institute of Technology in Biology and B.S. from Kanazawa University in Chemistry. After my Ph.D. I held a postdoc position in the Max-Planck Institute for Biophysiological Chemistry in Germany (Dr. Marty’s Lab) and studied synaptic transmission between cerebellar neurons. After that I began a circuit analysis in cerebral cortex and studied synaptic transmission and anatomical connections among cortical neurons at RIKEN and the National Institute for Physiological Sciences (Prof. Kawaguchi’s Lab). I then turned to the in vivo analysis of neuronal circuits with two-photon imaging of synapses of cortical neurons in live mice at Tokyo Medical and Dental University and The University of Tokyo (Prof. Okabe’s Lab). Further I developed two-photon imaging for functional analysis at Kyushu University and The University of Tokyo (Prof. Ohki’s Lab) and studied functional architecture of the mouse visual cortex.
For elucidation of the mechanisms underlying higher-order biological phenomena, e.g., intelligence and mental disorders in humans, comprehensive identification and quantitative analysis of human gene-networks and cellular circuits are required. Reverse genetics is one of the powerful methods for this elucidation. However, mouse genetics is generally low throughput, due to the need for repeat crossing of chimeras/mosaics to produce genetically modified mice, and hence analyzing many genes/cells is difficult. Recently, we have established an efficient method to produce mutant mice without crossing. We are developing a method to elucidate human biological phenomena by applying the high-throughput production method of our mutant mice to genetically humanized mice in which mouse genes are replaced with human genes.
Ukai H, Kiyonari H, Ueda HR. Embryonic stem cell-mouse protocol to produce knock-in (KI) mice in a single generation. Nature Protocols 2017 DOI 10.1038/nprot.2017.110
*Ode KL, *Ukai H, *Susaki EA, Narumi R, Matsumoto K, Hara J, Koide N, Abe T, Kanemaki MT, Kiyonari H, Ueda HR. Knockout-Rescue Embryonic Stem Cell-Derived Mouse Reveals Circadian-Period Control by Quality and Quantity of CRY1. Molecular Cell 2017 Jan 5;65(1):176-190. * These authors contributed equally to this work.
Susaki EA, Ukai H, Ueda HR. Next-generation mammalian genetics toward organism-level systems biology. npj. Syst. Biol. Appl. 2017 3, article number 15.
Ukai H. and Ueda HR. Systems Biology of Mammalian Circadian Clock. Annual Review of Physiology 2010 72:579-603.
*Isojima Y, *Nakajima M, *Ukai H, Fujishima H, Yamada RG, Masumoto KH, Kiuchi R, Ishida M, Ukai-Tadenuma M, Minami Y, Kito R, Nakao K, Kishimoto W, Yoo SH, Shimomura K, Takao T, Takano A, Kojima T, Nagai K, Sakaki Y, Takahashi JS, Ueda HR. CKIepsilon/delta-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock. Proc. Natl. Acad. Sci. USA. 2009 Sep 15;106(37):15744-9. * These authors contributed equally to this work.
*Ukai H, *Kobayashi TJ, Nagano M, Masumoto KH, Sujino M, Kondo T, Yagita K, Shigeyoshi Y, Ueda HR. Melanopsin-dependent photo-perturbation reveals desynchronization underlying the singularity of mammalian circadian clocks. Nature Cell Biology 2007 Nov;9(11):1327-34. * These authors contributed equally to this work.
*Sato TK, *Yamada RG, *Ukai H, Baggs JE, Miraglia LJ, Kobayashi TJ, Welsh DK, Kay SA, Ueda HR, Hogenesch JB. Feedback repression is required for mammalian circadian clock function. Nature Genetics 2006 Mar;38(3):312-9. * These authors contributed equally to this work.
I was a postdoctoral researcher at the National Institute of Radiological Sciences after earning a Ph.D. from the Graduate University for Advanced Studies. I developed the technologies for genome-scale analysis and discovered a new oncogenic mutation by using the technologies. Next, at the RIKEN CDB, I developed technologies for cellular-level systems biology using a circadian clock system as a model system of a complex phenomenon and elucidated the mechanism of the complex phenomenon such as the singularity behaviour of the circadian clock. After moved to the RIKEN QBiC, I started to develop the technologies toward organism-level systems biology to elucidate the mechanism of the higher-order biological phenomena, and have established an efficient method to produce mutant mice within a single generation. In my current position, by using my technology, I provide mutant mice and virus for researchers and also develop special mouse lines intended as common resources for the IRCN.
Human cognition is dynamic, and its underlying brain activity is unstable. Thus, neural fluctuations are essential for human intelligence and its development, while atypical brain dynamics should underpin neuropsychiatric disorders, including autism, schizophrenia and epilepsy. We pursue this framework and investigate biological mechanisms that link large-scale brain network architecture, global/local neural dynamics and typical/atypical cognition. We aim to utilise this research for the development of novel non-invasive treatment and diagnostic applications for a wide range of neuropsychiatric conditions.
Watanabe, T., G. Rees, and N. Masuda, Atypical intrinsic neural timescale in autism. (2019). eLife. 8.
Watanabe, T., et al., A Neuroanatomical Substrate Linking Perceptual Stability to Cognitive Rigidity in Autism. (2019). J Neurosci. 39, 6540.
Watanabe, T. and G. Rees, Brain network dynamics in high-functioning individuals with autism. (2017). Nat Commun. 8, 16048.
Watanabe, T., et al., Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. (2015). Brain. 138, 3400.
Watanabe, T., et al., Effects of rTMS of pre-supplementary motor area on fronto basal ganglia network activity during stop-signal task. (2015). J Neurosci. 35, 4813.
Aoki, Y. Watanabe, T. et al., Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial. (2015). Mol Psychiatry. 20, 447.
Watanabe, T., et al., Two distinct neural mechanisms underlying indirect reciprocity. (2014). Proc Natl Acad Sci USA. 111. 3990.
Watanabe, T., et al., Energy landscape and dynamics of brain activity during human bistable perception. (2014). Nat Commun. 5. 4765.
Watanabe, T., et al., Mitigation of socio-communicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity: a randomized trial. (2014). JAMA Psychiatry. 71,166.
Watanabe, T., et al., A pairwise maximum entropy model accurately describes resting-state human brain networks. (2013). Nat Commun. 4, 1370.
After medical training in The University of Tokyo (M.D., 2007) and its hospital, I completed a Ph.D. in the lab of Professor Yasushi Miyashita in the same university as a JSPS Research Fellow (2013). I conducted post-doctoral research with Professor Geraint Rees in University College London under JSPS and Marie-Curie Research Fellowships, respectively. In 2018, I was appointed Deputy Team Leader for the Miyashita lab in the RIKEN Center for Brain Science. I launched my lab in IRCN at UTokyo as an Associate Professor (UTokyo Excellent Young Researcher Program) in April 2020. Other career awards include the NeuroCreative Award and RIKEN Excellent Achievement Award.
Humans routinely learn new concepts, rules and strategies faster than the most powerful current deep learning algorithms. How does our brain achieve this? One possible key is that humans learn and store cognitive maps of our environments and maintain an array of causal models that organize incoming sensory inputs into these maps. These model-based cognitive maps can inform us whether and what type of information can be generalized from one situation to another, thus making new learning and memory more efficient. Our lab is interested in how cognitive maps and causal models are themselves learned. We use a variety of advanced computational models for human behavior and neural imaging data. We are also developing new machine learning algorithms inspired by the way humans learn, and, because much of our data is drawn from human fMRI, we develop novel algorithms for processing and understanding brain imaging data.
Cai, M. B., Schuck, N. W., Pillow, J. W., & Niv, Y. (2019). Representational structure or task structure? Bias in neural representational similarity analysis and a Bayesian method for reducing bias. PLoS Computational Biology, 15(5), e1006299.
Schuck, N. W., Cai, M. B., Wilson, R. C., & Niv, Y. (2016). Human orbitofrontal cortex represents a cognitive map of state space. Neuron, 91(6), 1402-1412.
Cai, M. B., Schuck, N. W., Pillow, J. W., & Niv, Y. (2016). A Bayesian method for reducing bias in neural representational similarity analysis. In Advances in Neural Information Processing Systems (pp. 4951-4959).
Cai, M. B., Eagleman, D. M., & Ma, W. J. (2015). Perceived duration is reduced by repetition but not by high-level expectation. Journal of Vision, 15(13), 19-19.
Cai, M. B., & Eagleman, D. M. (2015). Duration estimates within a modality are integrated sub-optimally. Frontiers in Psychology, 6, 1041.
In 2008 I received double B.S. degrees in Electronic and Information Science and Technology, and in Psychology from Peking University. In 2015 I completed a Ph.D. degree in Neuroscience from Baylor College of Medicine, studying the mechanism of time perception with David Eagleman and I obtained training in computational modeling from Wei Ji Ma. Subsequently, I was a postdoctoral researcher in Yael Niv’s lab at Princeton University, focusing on learning and decision making, and fMRI algorithms prior to joining IRCN in December 2019.
IRCN Deputy Director / Principal Investigator
Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo
Developmental Synapse Elimination in the Cerebellum,
Endocannabinoid-Mediated Modulation of Synaptic Transmission
The brain consists of neural circuits in which neurons are connected through numerous synapses. Information is transmitted at synapses from nerve endings to neurons by chemical substances called neurotransmitters. Therefore, studies on synaptic connectivity and function are crucial for the understanding of brain function. We investigate how the efficacy of synaptic transmission is regulated by endogenous cannabinoids (that is, substances in the brain which behave like cannabis) and how this regulation contributes to various brain functions. We also pursue how synaptic connectivity and function become matured during postnatal development. Specifically, we study the phenomenon known as synapse elimination or synapse pruning in which, among redundant immature synapses formed around birth, unnecessary connections are eliminated while functionally important ones are strengthened. We use the climbing fiber to Purkinje cell synapse in the cerebellum as a model to elucidate the mechanisms of developmental synapse elimination.
Postnatal development of synaptic wiring onto Purkinje cell of the cerebellum.
PC Purkinje cell, CF climbing fiber, GrC granule cell, PF parallel fiber, BC basket cell
Uesaka, N., Abe, M., Konno, K., Yamazaki, M., Sakoori, K., Watanabe, T., Kao, T-H., Mikuni, T., Watanabe, M., Sakimura, K. and Kano M. (2018) Retrograde signaling from progranulin to Sort1 counteracts synapse elimination in the developing cerebellum. Neuron 97: 796-805, 2018.
Choo, M., Miyazaki, T., Yamazaki, M., Kawamura, M., Nakazawa, T., Zhang, J., Tanimura, A., Uesaka, N., Watanabe, M., Sakimura, K. and Kano, M. (2017) Retrograde BDNF to TrkB signaling promotes synapse elimination in the developing cerebellum. Nat Commun 8: 195.
Uesaka, N., Uchigashima, M., Mikuni, T., Nakazawa, T., Nakao, H., Hirai, H., Aiba, A., Watanabe, M. and Kano, M. (2014) Retrograde semaphorin signaling regulates synapse elimination in the developing mouse brain. Science 344: 1020-1023.
Kano, M., Ohno-Shosaku, T., Hashimotodani, Y., Uchigashima, M. and Watanabe, M. (2009) Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89: 309-380.
Hashimoto, K. and Kano, M. (2003) Functional differentiation of multiple climbing fiber inputs during synapse elimination in the developing cerebellum. Neuron 38: 785-796.
Maejima, T., Hashimoto, K., Yoshida, T., Aiba, A. and Kano, M. (2001) Presynaptic inhibition caused by retrograde signal from metabotropic glutamate to cannabinoid receptors. Neuron 31: 463-475.
Ohno-Shosaku, T., Maejima, T. and Kano, M. (2001) Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals. Neuron 29: 729-738.
Kano, M., Hashimoto, K., Chen, C., Abeliovich, A., Aiba, A., Kurihara, H., Watanabe, M., Inoue, Y. and Tonegawa, S. (1995) Impaired synapse elimination during cerebellar development in PKCγ mutant mice. Cell 83: 1223-1231.
I received a M.D. from Tokyo Medical and Dental University in 1982, and earned a Ph.D. at the University of Tokyo, Graduate School of Medicine in 1986. I became a research associate at Jichi Medical School (Tochigi, Japan). In 1990, I joined the Max-Planck Institute for Biophysical Chemistry (Goettingen, Germany), as a visiting researcher. I returned to Jichi in 1992, and started to examine synapse elimination in the developing cerebellum. I moved to the RIKEN Institute (Wako, Japan) in 1995, and then became a professor of physiology at Kanazawa University, School of Medicine in 1998. In Kanazawa, my group discovered endocannabinoid-mediated retrograde suppression of synaptic transmission. In 2005, I moved to Osaka University, Graduate School of Medicine, and then moved back to the University of Tokyo, Graduate School of Medicine in 2007.
The human brain receives, processes, stores, and transmits complex information with great fidelity. The neuronal network that underlies these functions is comprised of an estimated 1011neurons linked by over 1014 synaptic connections between structurally and functionally different neurites, axons and dendrites. Precise pattering of dendrites as well as axons is essential for correct wiring and function of neural circuits. We combine genetics, imaging, and biochemical approaches to investigate the interplay between genetic and epigenetic control of neural morphogenesis, and deduce the functional importance of these regulatory systems in disease etiology, using the fruitfly and mouse as research models.
Yoshino J, Morikawa R, Hasegawa E and Emoto K (2017) Neural circuitry that evokes escape behavior in response to nociceptive stimuli in Drosophila larvae. Curr Biol 27: 2499-2504 (2017).
Yasunaga K, Tezuka A, Ishikawa N, Dairyo Y, Togashi K, Koizumi H and Emoto K (2015) Adult Drosophila sensory neurons specify dendrite boundaries independently of dendritic contacts through the Wnt5-Drl signaling pathway. Genes Dev 29: 1763-1775.
Kanamori, T., Yoshino, J., Yasunaga, K., Dairyo, Y., and Emoto, K. (2015) Local endocytosis triggers dendrite thinning and pruning in Drosophila sensory neurons. Nature Communications 6: 6515 (2015).
Kanamori, T., Kanai, M., Dairyo, Y., Yasunaga, K., Morikawa, R., and Emoto, K. (2013) Compartmentalized calcium transients trigger dendrite pruning in Drosophila sensory neurons. Science 340: 1475-1478.
Emoto, K., Parrish, J. Z., Jan, L., and Jan, Y. N. (2006) The tumour suppressor Hippo acts with the NDR kinases in dendritic tiling and maintenance. Nature 443: 210-213.
Emoto, K., He, Y., Ye, B., Grueber, W. B., Adler, P. N., Jan, L. Y., and Jan, Y. N. (2004) Control of dendritic branching and tiling by the Tricornered-kinase/Furry signaling pathway in Drosophila sensory neurons. Cell 119: 245-256.
I received a PhD from the Graduate School of Pharmaceutical Sciences, The University of Tokyo, working with Prof. Keizo Inoue. Postgraduate studies included work with Dr. Umeda at the Tokyo Metropolitan Institute of Medical Sciences and then with Profs. Yuh-Nung Jan & Lily Jan at the University of California San Francisco. In 2006, I became an investigator at the National Institute of Genetics and from 2010 served as Group Director, Osaka Bioscience Institute. In 2013 Professor, I joined the Graduate School of Sciences, The University of Tokyo and became the 10th head of a laboratory founded in 1877 by Prof. Edward Morse.
I have been studying mathematical theory for modelling complex systems and its wide-ranging transdisciplinary applications in science and technology from the viewpoint of mathematical engineering and chaos engineering. In particular, I developed a theoretical platform composed of (1) advanced control theory of complex systems, (2) complex network theory, and (3) nonlinear data analysis and data-driven modelling. On the applications side, I am working to bridge neuroscientific and clinical studies with next-generation AI by mathematical modeling and analyses of brain dynamics to realize neurointelligence.
Schäfer, B., Beck, C., Aihara, K., Witthaut, D. and Timme, M. (2018) Non-Gaussian Power Grid Frequency Fluctuations Characterized by Lévy-stable Laws and Superstatistics. Nature Energy 3(2):119-126.
McMahon, P.L., Marandi, A., Haribara, Y., Hamerly, R., Langrock, C., Tamate, S., Inagaki, T., Takesue, H., Utsunomiya, S., Aihara, K., Byer, R.L., Fejer, M.M., Mabuchi, H. and Yamamoto, Y. (2016) A Fully-programmable 100-spin Coherent Ising Machine with All-to-all Connections. Science 354(6312):614-617.
Inagaki, T., Haribara, Y., Igarashi, K., Sonobe, T., Tamate, S., Honjo, T., Marandi, A., McMahon, P.L., Umeki, T., Enbutsu, K., Tadanaga, O., Takenouchi, H., Aihara, K., Kawarabayashi, K., Inoue, K., Utsunomiya, S. and Takesue, H. (2016) A Coherent Ising Machine for 2000-node Optimization Problems. Science 354(6312):603-606.
Fujioka, E., Aihara, I., Sumiya, M., Aihara, K. and Hiryu, S (2016) Echolocating Bats Use Future-target Information for Optimal Foraging. Proc Natl Acad Sci USA 113(17):4848-4852.
Takahashi, N., Hirata, Y., Aihara, K. and Mas, P. (2015) A Hierarchical Multi-oscillator Network Orchestrates the Arabidopsis Circadian System. Cell 163(1):148-159.
Aihara, K., Imura, J. and Ueta, T.(Eds.) (2015) Analysis and Control of Complex Dynamical Systems: Robust Bifurcation, Dynamic Attractors, and Network Complexity. Springer Japan.
Aihara, K.(Ed.) (2010) Theory of Hybrid Dynamical Systems and its Applications to Biological and Medical Systems. Phil Trans Roy Soc A 368(1930).
Aihara, K. (2002) Chaos Engineering and its Application to Parallel Distributed Processing with Chaotic Neural Networks. Proc IEEE 90(5):919-930.
I received a B.E. degree in electrical engineering and Ph.D. degree in electronic engineering from the University of Tokyo (UTokyo), Tokyo, Japan, in 1977 and 1982, respectively. I led the ERATO (Exploratory Research for Advanced Technology) Aihara Complexity Modelling project for JST (Japan Science and Technology Agency) from 2003 to 2008 and the FIRST Innovative Mathematical Modelling project by JSPS (Japan Society for the Promotion of Science) through the FIRST (Funding Program for World-Leading Innovative R&D Science and Technology) program from 2010 to 2014 for CSTP (Council for Science and Technology Policy).
A fundamental question in understanding tissue development is how resident stem cells or multipotent progenitors give rise to the various cell types in appropriate numbers and at the right locations to achieve tissue organization. Our laboratory has been studying the mechanisms and logic that underlie the regulation of neural stem/progenitor cell fate both during embryonic brain development and in the adult brain. Our current research foci include the genetic and epigenetic regulation of neural stem/progenitor cell fate and neuronal maturation, the genesis and maintenance of adult neural stem cells, and the relevance of neural stem/progenitor cell dysregulation in neurodevelopmental disorders such as autism spectrum disorders.
Furutachi, S., Miya, H., Watanabe, T., Kawai, H., Yamasaki, N., Harada, Y., Imayoshi, I., Nelson, M., Nakayama, KI., Hirabayashi, Y., and Gotoh, Y. (2015) Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells. Nat. Neurosci. 18, 657-665.
Kishi, Y., Fujii, Y., Hirabayashi, Y. and Gotoh, Y. (2012) HMGA proteins regulate global chromatin state and the neurogenic potential in neocortical precursor cells. Nat. Neurosci. 15, 1127-1133.
Hirabayashi, Y., Suzki, N., Tsuboi, M., Endo, T.A., Toyoda, T., Shinga, J., Koseki, H., Vidal, M. and Gotoh, Y. (2009) Polycomb limits the neurogenic competence of neural precursor cells to promote astrogenic fate transition. Neuron 63, 600-613.
Ichijo, H., Nishida, E., Irie, K., ten Dijke, P., Saitoh, M., Moriguchi, T., Takagi, M., Matsumoto, K., Miyazono, K. and Gotoh, Y. (1997) Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science 275, 90-94.
Gotoh, Y., Nishida, E., Matsuda, S., Shiina, N., Kosako, H., Shiokawa, K., Akiyama, T., Ohta, K. & Sakai, H. (1991) In vitro effects on microtubule dynamics of purified Xenopus M phase-activated MAP kinase. Nature 349, 251-254.
Gotoh, Y., Nishida, E., Yamashita, T., Hoshi, M., Kawakami, M. & Sakai, H. (1990) MAP kinase activated by nerve growth factor and epidermal growth factor in PC12 cells. Identity with the mitogen-activated MAP kinase of fibroblastic cells. Eur. J. Biochem. 193, 661-669.
As a graduate student at the University of Tokyo and later as an Assistant Professor in Kyoto University where I led a group with Eisuke Nishida, our group purified and cloned the vertebrate MAP kinase (Erk) and its activator, MAP kinase kinase (Mek). I became fascinated by the beauty of the cell fate decision where, even using the same MAPK pathway, a cell can precisely decide whether it should proliferate or differentiate. After spending a few years in Jonathan Cooper’s laboratory in Seattle and Michael Greenberg’s laboratory in Boston where I learned the basics of brain development, I started a laboratory investigating neural stem/progenitor cell fate at the University of Tokyo at the Institute of Molecular and Cellular Biosciences in 2000. I was later appointed as a Professor at the same institute in 2005 and then in the Department of Pharmaceutical Sciences of the University of Tokyo in 2014.
Neuronal circuits made by synapses in the brain enable learning, memory, perception, emotion, and their impairment results in various mental disorders. We perform research that extensively utilize microscopic methods to observe cellular and molecular events deep within the brain, and which allow labeling of potentiated synapses and optical manipulation of synapses and circuits. We have shown that cerebral spine synapses undergo rapid enlargement during potentiation in the hippocampus, neocortex and basal ganglia. Such dynamic synaptic motilities are the sites of endogenous neuromodulation, therapeutic agents and addictive drugs. Moreover, the dynamic nature of synapses has allowed us to construct new optical and molecular probes for a better understanding of learning and cognition and their impairments.
Noguchi, J., Hayama, T., Watanabe, S., Ucar, H., Yagishita, S., Takahashi, N. & Kasai, H. (2016) State-dependent diffusion of actin-depolymerizing factor/cofilin underlies the enlargement and shrinkage of dendritic spines. Scientific Reports 6: 32897.
Hayashi-Takagi, A., Yagishita, S., Nakamura, M. Shirai, F., Wu, Y., Loshbaugh, A.L., Kuhlman, B., Hahn, K.M. and Kasai, H. (2015). Labelling and optical erasure of synaptic memory traces in the motor cortex. Nature 525:333-338.
Takahashi, N., Sawada, W., Noguchi, J., Watanabe, S., Ucar, H., Hayashi-Takagi, A., Yagishita, S., Ohno, M., Tokumaru, H. & Kasai, H. (2015). Two-photon fluorescence lifetime imaging of primed SNARE complexes in presynaptic terminals and beta cells.
Nature Comm. 6:8531.
Yagishita, S., Hayashi-Takagi, A., Ellis-Davies, G.C.R., Urakubo, H., Ishii, S. & Kasai, H. (2014). A critical time window for dopamine action on the structural plasticity of dendritic spines. Science 345:1616-1620.
Hayama, T., Noguchi, J., Watanabe, S., Ellis-Davies, G.C.R., Hayashi, A., Takahashi, N., Matsuzaki, M. & Kasai, H. (2013). GABA promotes the competitive selection of dendritic spines by controlling local Ca2+ signaling. Nature Neurosci 16:1409-1416.
Tanaka, J., Horiike, Y., Matsuzaki, M., Miyazaki, T., Ellis-Davies, G.C.R. & Kasai, H. (2008). Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Science 319:1683-1687.
Matsuzaki, M., Honkura, N., Ellis-Davies, G.C.R. & Kasai, H. (2004). Structural basis of long-term potentiation in single dendritic spines. Nature 429:761-766.
I graduated from the University of Tokyo School of Medicine and became a Humboldt fellow in the Max-Planck Institute, Germany. After coming back to Japan, I was an Assistant and then Associate Professor of the Physiology Department of the University of Tokyo, and promoted to Professor of the National Institute of Physiological Sciences, Okazaki. Currently, I have been developing optical methods (two-photon uncaging of caged-glutamate), and revealed that synaptic morphology shows a tight correlation with connectivity, and synapses rapidly enlarge when learning stimuli are given to enhance connectivity. I then moved to the Center for Disease and Integrative Medicine in the University of Tokyo, where I have been pursuing optical and molecular investigations of learning and memory in the brain and its related psychiatric disorders.
My research focuses on the biological mechanisms underlying psychosis onset and the development of effective early intervention strategies. Our group’s expertise includes a wide range of neuroimaging techniques, such as magnetic resonance imaging (MRI), MR spectroscopy, EEG, MEG, and near-infrared spectroscopy (NIRS). We extended our studies to adolescent brain neuroscience via the launch of the Tokyo TEEN Cohort in 2012, which is the first large-scale population-based cohort study of adolescents in Asia. I am also a principal investigator of the clinical research group of Japan’s national brain project called Brain/MINDS, organizing an all-Japan multi-site MRI research framework in psychiatric disorders, applying EEG methodology to non-human primates.
Kasai K, et al: Strengthening community mental health services in Japan. Lancet Psychiatry 4: 268-270, 2017. (Viewpoint)
Kasai K, Fukuda M: Science of recovery in schizophrenia research: brain and psychological substrates of personalized value. npj Schizophrenia 3: 14, 2017. (editorial)
Okano H, et al: Brain/MINDS: A Japanese national brain project for marmoset neuroscience. Neuron 92: 582-590, 2016. (Viewpoint)
Okada N, et al: Abnormal asymmetries in subcortical brain volume in schizophrenia. Mol Psychiatry 21: 1460-1466, 2016.
Yahata N, et al: A small number of abnormal brain connections predicts adult autism spectrum disorder. Nat Commun 7: 11254, 2016.
Takizawa R, Fukuda M, Kawasaki S, Kasai K, Mimura M, Pu S, Noda T, Niwa SI, Okazaki Y: Neuroimaging-aided differential diagnosis of the depressive state. Neuroimage. 85:498-507, 2014
Nagai T, Tada M, Kirihara K, Araki T, Jinde S, Kasai K: Mismatch negativity as a “translatable” brain marker toward early intervention for psychosis: a review. Front Psychiatry 4:1-10, 2013
Kasai K, Shenton ME, Salisbury DF, Hirayasu Y, Onitsuka T, Spencer M, Yurgelun-Todd D, Kikinis R, Jolesz FA, McCarley RW: Progressive decrease of left Heschl gyrus & planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Arch Gen Psychiatry 60(8):766-775, 2003.
I earned an M.D. in 1995 and Ph.D. in Psychiatry in 2004, both from the University of Tokyo. I gained experience at the University of Tokyo Hospital and National Center of Neurology and Psychiatry, before an appointment as visiting instructor at Harvard Medical School, USA, from 2000 to 2002. I returned to the University of Tokyo Hospital, Department of Neuropsychiatry in 2002 as Instructor, and was appointed Lecturer in 2003 and Professor and Chair of the Department of Neuropsychiatry in 2008. I was a recipient of the Distinguished Investigator Award from the Japanese Society of Biological Psychiatry in 2003, and the Young Investigator Award from the Japan Neuroscience Society in 2008.
Institute of Neuroscience Technische Universität München
Mechanisms of Synaptic Interactions in Neuronal Circuits
Our current research is focused on the development and application of methods that allow a quantitative understanding of function and dysfunction of neurons and circuits in the intact brain. Previously, our team pioneered in vivo two-photon calcium imaging of cortical circuits with single cell resolution. More recently, we developed the LOTOS (low power temporal oversampling) method of high-resolution two-photon calcium imaging and used it for the functional mapping of dendritic spines in vivo. These approaches are used in the lab for the exploration of behavior-determined synaptic signaling and dendritic signal integration in neurons of defined brain circuits. A major goal is a better understanding of the cellular and circuit mechanisms of learning and memory in the healthy brain, especially in the developing and the mature cerebellum. In the diseased brain, we explore the pathophysiology underlying the impairment of cognition and memory in Alzheimer’s disease.
Edwards F, Konnerth A, Sakmann B and Takahashi T (1989) A thin slice preparation for patch clamp recordings from neurones of the mammalian central nervous system. Pflügers Archiv 414, 600-612.
Kano M, Rexhausen U, Dreessen J and Konnerth A (1992) Synaptic excitation produces a long-lasting rebound potentiation of inhibitory synaptic signals in cerebellar Purkinje cells. Nature 356, 601-604.
Takechi H, Eilers J and Konnerth A (1998) A new class of synaptic response involving calcium release in dendritic spines. Nature 396, 757-760.
Stosiek C, Garaschuk O, Holthoff K and Konnerth A (2003) ‘In vivo’ two-photon calcium imaging of neuronal networks. Proc Nat Acad Sci USA 100, 7319-7324.
Chen X, Leischner U, Rochefort NL, Nelken I and Konnerth A (2011) Functional mapping of single spines in cortical neurons in vivo. Nature 475, 501-505.
Grienberger C and Konnerth A (2012) Imaging Calcium in Neurons. Neuron 73, 862-885.
Hartmann J, Karl RM, Adelsberger H, Brill MS, Rühlmann C, Ansel A, Sakimura S, Baba Y, Kurosaki T, Misgeld T and Konnerth A (2014) STIM1 controls neuronal Ca2+ signaling, mGluR1-dependent synaptic function and cerebellar motor behavior. Neuron 82, 635–644.
Zott B, Busche MA, Sperling R and Konnerth A (2018) What Happens with the Circuit in Alzheimer's Disease in Mice and Humans? Annual Reviews Neuroscience 41, 277-297.
I graduated (M.D.) from the Ludwig-Maximilians University Munich in Germany and am currently a Hertie Senior Professor of Neuroscience at the Institute for Neuroscience at the Technical University of Munich and a Principal Investigator at the International Research Center for Neurointelligence. I am a member of the German National Academy of Sciences Leopoldina, the Academia Europaea and the Bavarian Academy of Sciences. In 2015 I shared the Brain Prize with Winfried Denk, Karel Svoboda and David Tank.
I am interested in visual neuroscience and functional brain mapping. In 2005, I developed a method of single-cell resolution functional mapping with two-photon calcium imaging, and was able to measure the orientation selectivity of hundreds of neurons in visual cortex revealing the functional architecture of visual cortex between rodents and higher mammals (Ohki et al., 2005, Nature). In 2006, using this method, I solved a long-standing problem in visual neuroscience - the micro-architecture of pinwheel centers at the single-cell level (Ohki et al., 2006). In 2012, I found that neurons derived from the same neural stem cells tend to acquire similar orientation selectivity in the adult mouse visual cortex (Ohtsuki et al., 2012) and later that neuronal activity is not required for the initial formation of orientation selectivity, but required for the later reorganization (Hagihara et al., 2015). Our lab continue to study the interplay between innate circuits determined by the developmental programs, and neuronal activity in determining the functions of neurons in the cerebral cortex.
Matsui T, Murakami T, Ohki K. Transient neuronal coactivations embedded in globally propagating waves underlie resting-state functional connectivity. Proc Natl Acad Sci U S A. 113:6556-61 (2016).
Kondo S, Ohki K. Laminar differences in the orientation selectivity of geniculate afferents in mouse primary visual cortex. Nat Neurosci.,19: 316-9 (2016).
Hagihara KM, Murakami T, Yoshida T, Tagawa Y, Ohki K. Neuronal activity is not required for the initial formation and maturation of visual selectivity. Nat Neurosci.,18: 1780-8 (2015).
Kawashima T, Kitamura K, Suzuki K, Nonaka M, Kamijo S, Takemoto-Kimura S, Kano M, Okuno H, Ohki K, Bito H. Functional labeling of neurons and their projections using the synthetic activity-dependent promoter E-SARE. Nat Methods. 10: 889-895 (2013).
Ohtsuki G, Nishiyama M, Yoshida T, Murakami T, Histed MH, Lois C, Ohki K Similarity of visual selectivity among clonally related neurons in visual cortex. Neuron. 75: 65-72 (2012).
T. Mrsic-Flogel, S. B. Hofer, K. Ohki, R. C. Reid, T. Bonhoeffer, M. Hubener. Homeostatic regulation of eye-specific responses in visual cortex during ocular dominance plasticity. Neuron. Vol. 54:961-72 (2007).
Ohki K, Chung S, Kara P, Hubener M, Bonhoeffer T, Reid RC. Highly ordered arrangement of single neurons in orientation pinwheels. Nature 442: 925-928 (2006).
Ohki K, Chung S, Ch'ng YH, Kara P, Reid. RC Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex. Nature 433: 597-603 (2005).
Ohbayashi M, Ohki K, Miyashita Y. Conversion of working memory to motor sequence in the monkey premotor cortex. Science 301: 233-6 (2003).
H. Kikyo, K. Ohki, Y. Miyashita. Neural correlates for feeling-of-knowing: an fMRI parametric analysis. Neuron 36: 177-86 (2002).
1990-1996 Medical student, Faculty of Medicine, The University of Tokyo (MD)
1996-2000 PhD student, Department of Physiology, The University of Tokyo (PhD)
1996-1996 Visiting scholar, Department of Brain and Cognitive Sciences, MIT
2000-2002 Assistant Professor, Department of Physiology, The University of Tokyo
2002-2008 Research Fellow, Department of Neurobiology, Harvard Medical School
2008-2010 Instructor, Department of Neurobiology, Harvard Medical School
2010-2016 Professor, Department of Molecular Physiology, Kyushu University
2016-today Professor, Department of Physiology, The University of Tokyo
Our work has focused on in vitro studies of single molecule motors, combining single molecule imaging, gene manipulation, and structural biology techniques. Currently we are attempting to extend our methods to observe such functions intracellularly to confirm the regulating mechanism(s). Motor proteins transport a variety of elements inside the cell. We are also studying the navigation system by directly observing transportation using new imaging techniques and the motor protein kinesin KIF5, a key regulator for axonal development, as our model. Despite neurons extending a large number of projections, only one becomes an axon. Recently, we have discovered that the structures of the microtubules on which kinesins travel in dendrites and the axon are different. KIF5 can recognize the structural difference between these microtubules and therefore be used to determine which neural projections become the axon and which become dendrites.
Hayashi K, Tsuchizawa Y, Iwaki M, Okada Y. Application of the fluctuation theorem for non-invasive force measurement in living neuronal axons. Molecular Biology of the Cell, 2018 in press
Shima T, Morikawa M, Kaneshiro J, et al. Kinesin-binding triggered conformation switching of microtubules contributes to polarized transport. Journal of Cell Biology 2018, in press
Grzybowski M, Taki M, Senda K, et al. A Highly Photostable Near‐infrared Labeling Agent Based on a Phospha‐rhodamine for Long-term and Deep Imaging. Angewandte Chemie International Edition 2018 doi:10.1002/anie.201804731
Komatsu N, Terai K, Imanishi A, et al. A platform of BRET-FRET hybrid biosensors for optogenetics, chemical screening, and in vivo imaging. Scientific Report 9:8984 (2018)
Takeshima T, Takahashi T, Yamashita J, Okada Y, Watanabe S. A multi-emitter fitting algorithm for potential live cell super-resolution imaging over a wide range of molecular densities. Journal of Microscopy (2018) doi:10.1111/jmi.12714
Nozaki T, Imai R, Tanbo M, et al. Dynamic Organization of Chromatin Domains Revealed by Super-Resolution Live-Cell Imaging. Molecular Cell 67: 282-293 (2017)
Takai A, Nakano M, Saito K, et al. Expanded palette of Nano-lanterns for real-time multicolor luminescence imaging. Proceedings of the National Academy of Sciences of the United States of America 112(14). 4352-4356 (2015) doi: 10.1073/pnas.1418468112
Hayashi S, Okada Y. Ultrafast superresolution fluorescence imaging with spinning disk confocal microscope optics. Molecular Biology Of The Cell 26(9). 1743-1751 (2015) doi: 10.1091/mbc.E14-08-1287
Okada Y, Nakagawa S. Super-resolution imaging of nuclear bodies by STED microscopy. Methods in Molecular Biology 1262. 21-35 (2015) doi: 10.1007/978-1-4939-2253-6_2
Uno S, Kamiya M, Yoshihara T, et al. A spontaneously blinking fluorophore based on intramolecular spirocyclization for live-cell super-resolution imaging. Nature Chemistry 6(8). 681-689 (2014) doi: 10.1038/nchem.2002
Yajima H, Ogura T, Nitta R, et al. Conformational changes in tubulin in GMPCPP and GDP-taxol microtubules observed by cryoelectron microscopy. Journal of Cell Biology 198(3). 315-322 (2012) doi: 10.1083/jcb.201201161
I graduated from The University of Tokyo, Faculty of Medicine in 1993 and obtained a medical license. After a JSPS research fellow at the Graduate School of Medicine, The University of Tokyo, I became a research associate at the same university. I moved to RIKEN in 2011 as a Team Leader in the Quantitative Biology Center. In 2016, I was invited to my current professor position in the Department of Physics, The University of Tokyo with a cross-appointment at RIKEN. Now, my lab continues our studies on the physiological functions and mechanisms of a molecular motor, kinesin, by combining a wide variety of imaging techniques such as single molecule imaging, cryo-EM, X-ray crystallography, and fluorescent live cell imaging, including single-molecule imaging and super-resolution microscopy.
Department of Complexity Science and Engineering, Graduate School of Frontier Sciences, The University of Tokyo
Department of Computer Science, Graduate School of Information Science and Technology, The University of Tokyo
Artificial Intelligence and Machine Learning
Machine learning is aimed at developing a computer that learns like humans. State-of-the-art machine learning technologies, which are based on statistical processing of big data by powerful computers, are highly successful in various real-world problems such as speech recognition, image understanding, and natural language translation. However, humans do not require big data or an enormous computational power to acquire intelligence and thus there is still a significant gap between machine learning and human learning. The goal of my research is to construct neuro-inspired machine learning paradigms that can fill the gap between artificial intelligence and human intelligence and establish a foundation of next-generation intelligent data processing technologies.
Hu, W., Niu, G., Sato, I., & Sugiyama, M. Does distributionally robust supervised learning give robust classifiers? In Proceedings of 35th International Conference on Machine Learning (ICML2018), pp.2029-2037, 2018.
Kiryo, R., du Plessis, M. C., Niu, G., & Sugiyama, M. Positive-unlabeled learning with non-negative risk estimator. In Advances in Neural Information Processing Systems 30, pp.1674-1684, 2017.
Sugiyama, M. Introduction to Statistical Machine Learning, Morgan Kaufmann, 2015.
Sugiyama, M. Statistical Reinforcement Learning: Modern Machine Learning Approaches, Chapman and Hall/CRC, 2015.
Sugiyama, M., Suzuki, T., & Kanamori, T. Density Ratio Estimation in Machine Learning, Cambridge University Press, 2012.
Sugiyama, M. & Kawanabe, M. Machine Learning in Non-Stationary Environments: Introduction to Covariate Shift Adaptation, MIT Press, 2012.
Sugiyama, M. Dimensionality reduction of multimodal labeled data by local Fisher discriminant analysis. Journal of Machine Learning Research, vol.8 (May), pp.1027-1061, 2007.
I received the degrees of Bachelor, Master, and Doctor of Engineering in Computer Science from Tokyo Institute of Technology, Japan in 1997, 1999, and 2001, respectively. In 2001, I was appointed Assistant Professor in the same institute, and I was promoted to Associate Professor in 2003. Then I moved to the University of Tokyo as Professor in 2014. Since 2016, I have concurrently served as the Director of the RIKEN Center for Advanced Intelligence Project. I received the Japan Society for the Promotion of Science Award and the Japan Academy Medal in 2017. My research interests include theories and algorithms of machine learning and data mining, and a wide range of applications such as signal processing, image processing, and robot control.
Department of Mechano-Informatics, Graduate School of Information Science and Technology, The University of Tokyo Department of Mechanical and Biofunctional Systems, Institute of Industrial Science, The University of Tokyo
Biohybrid systems, Micro electro mechanical systems,
Microfluidics, Tissue Engineering, Artificial cell membrane
Our group focuses on the design and fabrication of bio-hybrid systems that combine bio functional materials with micro/nano devices. The development of microfabrication technologies has realized ultrasmall sensors and actuators at micro and nanometer scale, although the real biological systems are often more sensitive, efficient and functional than the micromachines. One idea to solve this problem is to create hybrid systems by fusing the mechanical components with biomaterials such as biological cells and molecular machines. For example, we have succeeded in the fabrication of microelectrodes which have small microfluidic channels using a flexible polymer to stimulate neural cells chemically and detect neural signals electrically. Biohybrid neural probes which can connect artificial systems and brain will contribute to a better understanding of our brain.
Yuya Morimoto, Hiroaki Onoe and Shoji Takeuchi: Biohybrid robot powered by an antagonistic pair of skeletal muscle tissues. Science Robotics, vol. 3, eaat4440, 2018
Koki Kamiya, Ryuji Kawano, Toshihisa Osaki, Kazunari Akiyoshi, and Shoji Takeuchi:Cell-sized asymmetric lipid vesicles facilitate the investigation of asymmetric membranes, Nature Chemistry, vol. 8, pp. 881-889, 2016
Shigenori Miura, Koji Sato, Midori Kato-Negishi, Tetsuhiko Teshima and Shoji Takeuchi: Fluid shear triggers microvilli formation via mechanosensitive activation of TRPV6, Nature Communications, vol. 6, 8871, 2015
Won Chul Lee, Kwanpyo Kim, Jungwon Park, Jahyun Koo, Hu Young Jeong, Hoonkyung Lee, David Weitz, Alex Zettl, and Shoji Takeuchi: Graphene-templated directional growth of an inorganic nanowire, Nature Nanotechnology, vol. 10, pp. 423-428, 2015
Hiroaki Onoe, Teru Okitsu, Akane Itou, Midori Kato-Negishi, Riho Gojo, Daisuke Kiriya, Koji Sato, Shigenori Mirua, Shintaroh Iwanaga, Kaori Kuribayashi-Shigetomi, Yukiko Matsunaga, Yuto Shimoyama, and Shoji Takeuchi: Metre-long Cell-laden Microfibres Exhibit Tissue Morphologies and Functions, Nature Materials, vol.12, pp. 584-590, 2013
Yun Jung Heo, Hideaki Shibata, Teru Okitsu, Tetsuro Kawanishi, and Shoji Takeuchi: Long-term in vivo glucose monitoring using fluorescent hydrogel fibers, Proc. Natl. Acad. Sci. USA, vol. 108(33), pp. 13399-13403, 2011
Hideaki Shibata, Yun Jung Heo, Teru Okitsu, Yukiko Matsunaga, Tetsuro Kawanishi, and Shoji Takeuchi: Injectable hydrogel microbeads for fluorescence-based continuous glucose monitoring,Parylene-coating in PDMS microfluidic channels prevents the absorption of fluorescent dyes, Proc. Natl. Acad. Sci. USA,vol. 107, no. 42, pp. 17894-17898, 2010
N. Misawa, H. Mitsuno, R. Kanzaki, and S. Takeuchi: A Highly Sensitive and Selective Odorant Sensor using Living Cells Expressing Insect Olfactory Receptors, Proc. Natl. Acad. Sci. USA , vol. 107(35), pp. 15340-15344, 2010
Wei-Heong TAN and Shoji TAKEUCHI: A Trap-and-Release Integrated Microfluidic System for Dynamic Microarray Applications, Proc. Natl. Acad. Sci. USA, vol. 104, no. 4, pp. 1146-1151, 2007
I received the B.E., M.E., and Dr. Eng. degrees in mechanical engineering from the University of Tokyo, Tokyo, Japan in 1995, 1997, and 2000, respectively. Currently, I am a Professor and Director of the Center for International Research on Integrative Biomedical Systems (CIBiS), Institute of Industrial Science (IIS) at the University of Tokyo. My team and I have authored more than 160 peer-reviewed publications and filed over 70 patents, and I have been recognized with honors, including the MEXT Young Scientists' Prize in 2008, the JSPS prize in 2010, and the ACS Analytical Chemistry Young Innovator Awards in 2015. My current research interests include 3D tissue fabrication, implantable devices, artificial cells/lipid bilayer systems, and biohybrid MEMS.
The brain’s neuronal circuits are shaped by sensory experiences from the environment in early life. The wiring of neuronal circuits in this early critical period are essential to control the later development of higher cognitive functions. As human babies learn to speak from what they hear, songbirds learn to sing from what they listen to in the critical period developmental time window. Songbird song learning from auditory experiences include many interesting questions such as: how do they detect their own species songs and learn from them? How can they selectively learn from specific birds, normally their fathers, from the variety of songs they hear? Why do they learn only during a specific period of time during development? Our lab is tackling these questions and hope to understand how our nascent brain circuits make such intelligence possible.
Yanagihara S. and *Yazaki-Sugiyama Y. (2018) Social interaction with a tutor modulates responsiveness of specific auditory neurons in juvenile zebra finches. Behav Proc, doi: 10.1016/j.beproc.2018.04.003
Araki M., Bandi M. M. and *Yazaki-Sugiyama Y. (2016) Mind the Gap: Neural Coding of Species Identity in Birdsong Prosody. Science 354: 1282-1287 Featured: Science 354: 1234-1235
Yanagihara S. and *Yazaki-Sugiyama Y. (2016) Auditory experience dependent cortical circuit shaping for memory formation in bird song learning. Nat. Commun, doi: 10.1038/NCOMMS11946. (featured article)
*Yazaki-Sugiyama Y., Yanagihara S, Fuller P.M. and Lazarus M. (2015) Acute inhibition of a cortical motor area impairs vocal control in singing zebra finches. Eur J Neuroscience 41:97-108
Yazaki-Sugiyama Y., Kang S., Câteau H., Fukai T. and *Hensch T.K. (2009) Bidirectional plasticity in fast-spiking GABA circuits by visual experience. Nature 462: 218-221
Yazaki-Sugiyama Y. and *Mooney R. (2004) Sequential learning from multiple tutors and serial retuning of auditory neurons in a brain area important to birdsong learning. J Neurophysiol 92: 2771-2788
Focused by editor; J Neurophysiol 92 2642-2643 (2004)
I earned a Ph.D. from Sophia University on the neuroethological studies of quail vocal behavior. I started songbird study at my first postdoctoral fellowship in Rich Mooney’s lab at Duke University and then examined critical period neuronal mechanisms at Takao Hensch’s lab at the RIKEN Brain Science Institute before moving to an independent position at the Okinawa Institute of Science and Technology (OIST) Graduate University and subsequently to The University of Tokyo.