Project of Publicly Offered Research

A01: Fundamental research on generative brain systems for human individuality

The effect of VMAT1 variants and the experiences on individual differences of emotion.

photo:Masakado Kawata
Project leader

Graduate School of Life Sciences
Professor Masakado Kawata

Further information

Message from Project leader

It has been suggested that the evolution of human specific social behavior and cognitive ability had caused psychiatric disorders. On the other hand, in many cases, these psychiatric disorders-relevant genes show allelic polymorphisms, which could contribute to a human personality. Thus, we focus on psychiatric disorders-relevant genes which have been subject to positive natural selection through evolutionary lineages from nonhuman species and these genes in which allelic polymorphisms are maintained by balancing selection in the present human population. We could understand the mechanisms of the evolution of human mental personality by examining the cause of maintenance of these alleles and the effect of the allelic differences on mental differences.
Our previous study showed that out of 1,013 psychiatric disorders-relevant genes, VMAT1 could be detected as a positively selected gene in human lineage. Among them, VMAT1, vesicular monoamine transporter 1, is particularly interesting since it has a human-unique polymorphism (Thr/Ile) in the 136th amino acid site compared to other mammals (Asn). This, in this project, we will try to examine the cause of the maintenance of polymorphism of VMAT1 by using Tohoku Megabank database for genomic and mental condition data. In addition, we will examine the phenotypic effects of this allelic polymorphism by creating genome editing mice.

  • Project leader
    ProfessorMasakado Kawata

    Graduate School of Life Sciences

    Research Area:
    Evolutionary Biology

    E-mail:
    kawata*m.tohoku.ac.jp
    (Please convert "*" into "@".)

    URL:
    http://meme.biology.tohoku.ac.jp/klabo-wiki/

Selected Publication
  • Takahashi, Y., Y. Suyama, Y. Matsuki, R. Funayama, K. Nakayama and M. Kawata. Lack of genetic variation prevents adaptation at the geographic range margin in a damselfly. Molecular Ecology 25 , 4450-4460, 2016
  • Akashi, H. D., A. Cadiz, S. Shigenobu, T. Makino and M. Kawata. Differentially expressed genes associated with adaptation to different thermal environments in three sympatric Cuban Anolis lizards. Molecular Ecology, 25, 2273-2285, 2016
  • Wallberg, A., F. Han, G. Wellhagen, B. Dahle, M. Kawata, N. Haddad, Z. L. P. Simões,, M. H. Allsopp, I. Kandemir, P. D. la Rúa, C.W. Pirk, and M. T. Webster. A worldwide survey of genome sequence variation provides insight into the evolutionary history of the honeybee Apis mellifera. Nature Genetics 46, 1081–1088, 2014
  • Takahashi, Y., K. Kagawa, E. I. Svensson and M. Kawata. Evolution of increased phenotypic diversity enhances population performance by reducing sexual harassment in damselflies. Nature Communications 5, 4468, 2014
  • Tamate, S., M. Kawata and T. MakinoContribution of non-ohnologous duplicated genes to high habitat variability in mammals. Molecular Biology and Evolution 31 ,1779-1786, 2014
  • Tezuka, A., S. Kasagi, C. van Oosterhout, M. McMullan?, W. M. Iwasaki, D. Kasai, M. Yamamichi, H. Innan, S. Kawamura, and M. Kawata. Divergent selection on opsin gene variation in guppy (Poecilia reticulata) populations of Trinidad and Tobago. Heredity 113, 381–389, 2014
  • Makino, T., McLysaght, A. and M. Kawata. Genome-wide deserts for copy number variation in vertebrates. Nature Communications 4:2283, 2013
  • Makino, T. and M. Kawata. Habitat variability correlates with duplicate content of Drosophilagenomes. Molecular Biology and Evolution, 29, 3169-3179, 2014
  • Bridle, J. R., J. Polechova, M. Kawata, R. K. Butlin (2010) Why is adaptation prevented at ecological margins? New insights from individual-based simulations. Ecology Letters 13, 485-494, 2010.
  • Tsuda, E. M. and M. Kawata (2010) Evolution of gene regulatory networks by fluctuating selection and intrinsic constraints. PLoS Computational Biology 6(8): e1000873, 2010

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Individual difference model integrating behavior, brain mechanisms, and genes.

photo:Koji Jimura
Project leader

Department of Biosciences and Informatics, Keio University
Associate Professor Koji Jimura

Further information

Message from Project leader

I have been aiming to understand brain mechanisms implementing sophisticated human mental functions by exploring brain mechanisms involved in behavioral situations. Particular interests have focused on brain-wide mechanisms well developed in humans, such as executive control and economic decision-making using non-invasive neuroimaging techniques, mainly functional MRI. Some of my prior work has assumed that examination of individual differences in behavioral characteristics and brain functions allows us to elucidate the sophisticated human brain mechanisms.
Conventional standard fMRI studies have first made a hypothesis, then designed behavioral tasks, and performed fMRI experiments. This study approach is powerful to examine specific mental mechanisms, but small sample size and restricted tested hypotheses entailed limited reliability and detectability. Then the current study analyzes open resource datasets involving huge samples of consistent behavioral assessments and fMRI experiments from individuals, in order to examine individual differences in brain mechanisms and behavioral characteristics. The current study also aim to develop a model that comprehensively explains genes, brain mechanisms, and behaviors by integrating open resource datasets that provide brain-gene relations. Then I wish to challenge to draw individuals’ characteristics that extend prior knowledge about specific brain-behavior mechanisms identified by the conventional approach.

  • Project leader
    Associate ProfessorKoji Jimura

    Department of Biosciences and Informatics, Keio University

    Research Area:
    Cognitive Neuroscience, Neuroinformatics

    E-mail:
    jimura*bio.keio.ac.jp
    (Please convert "*" into "@".)

    URL:
    http://keio.jimuralab.org/

Selected Publication
  • Jimura K, Chushak MS, Westbrook A, Braver TS: Intertemporal decision-making involves prefrontal control mechanisms associated with working memory. Cerebral Cortex, doi:10.1093/cercor/bhx015, 2017.
  • Jimura K, Hirose S, Kumimatsu K, Ohtomo K, Koike Y, Konishi S: Late enhancement of brain-behavior correlations during response inhibition. Neuroscience, 274, 383-392, 2014.
  • Jimura K, Cazalis F, Stover ER, Poldrack RA: The neural basis of task switching changes with skill acquisition. Frontiers in Human Neuroscience, 8, 339, 2014.
  • Jimura K, Chushak SM, Braver TS: Impulsivity and self-control during intertemporal decision-making linked to the neural dynamics of reward value representation. Journal of Neuroscience, 33, 344-357, 2013.
  • Jimura K, Poldrack RA: Analyses of regional-average activation and multivoxel pattern information tell complementary stories. Neuropsychologia, 50, 544-552, 2012.
  • Jimura K, Myerson J, Hilgard J, Keighley J, Braver TS, Green L: Domain independence and stability in young and old adults’ discounting of delayed rewards. Behavioural Processes, 87, 253-259 2011.
  • Jimura K, Braver TS: Age-related brain activity dynamics during task switching. Cerebral Cortex, 20, 1420-1431 2010.
  • Jimura K, Locke HS, Braver TS: Prefrontal cortex mediation of cognitive enhancement in rewarding motivational contexts. Proceedings of National Academy Sciences of the USA, 107, 8871-8876, 2010.
  • Jimura K, Konishi S, Asari T, Miyashita Y: Temporal pole activity during understanding other persons’ mental state correlated with neuroticism trait. Brain Research, 1328, 104-112 2010.
  • Jimura K, Myerson J, Hilgard J, Braver TS, Green L: Are people really more patient than other animas? Evidence from human discounting of real liquid rewards. Psychonomic Bulletin and Review, 16, 1071-1075, 2009.
  • Jimura K, Konishi S, Miyashita Y: Temporal pole activity during perception of sad faces but not happy faces correlates with neuroticism trait. Neuroscience Letters, 453, 45-48, 2009.

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Neural bases of individual differences in cognition: clinical study of brain-damaged patients

photo:Kyoko Suzuki
Project leader

Division of Neurology and Clinical Neuroscience, Third Department of Internal Medicine, Yamagata University Graduate School of Medicine
Professor Kyoko Suzuki

Further information

Message from Project leader

Individuals differ in the ability of language, which must be underpinned by differences in brain functioning. Lesions in the language-related area result in aphasic syndromes that vary from patient to patient despite similar lesion site. We aim to find neural bases of individual differences in cognition using mapping with electrocortical stimulation and clinicoradiological study of brain-damaged patients.
Intraoperative language mapping in an awake craniotomy has revealed that the cortical and subcortical regions whose stimulation inhibited language processing are different among patients. In addition, task-related high gamma-band activity in electrocorticograms was observed at anatomically different sites in each patient during a verb generation task.
Primary progressive aphasia (PPA) is a syndrome in which degeneration of language-related areas is associated with progressive deficits in language function. Patients with PPA demonstrated different course of progression, which might be related to an individual difference in degenerative areas. We will investigate the neural correlates of the individual difference in language deficits that can be observed in PPA by neuroradiological techniques.

  • Project leader
    ProfessorKyoko Suzuki

    Division of Neurology and Clinical Neuroscience, Third Department of Internal Medicine, Yamagata University Graduate School of Medicine

    Research Area:
    Neurology, Neuropsychology

    E-mail:
    kyon*med.id.yamagata-u.ac.jp
    (Please convert "*" into "@".)

    URL:
    http://www.id.yamagata-u.ac.jp/Higherbrain/index.html

Selected Publication
  • Suzuki K, Yamadori A, Endo K, Fujii T, Ezura M, Takahashi A. Dissociation of letter and picture naming from callosal disconnection. Neurology 51:1390-1394, 1998
  • Suzuki K, Otsuka Y, Endo K, Fujii T, Yamadori A. Visuospatial deficits due to impaired visual attention: Investigation of two cases of slowly progressive visuospatial impairment. Cortex 39:327-342, 2003
  • Tanji K, Suzuki K, Delorne A, Shamoto H, Nakasato N. High-frequency gamma band activity in the basal temporal cortex during picture naming and lexical decision tasks. Journal of Neuroscience 25:3287-3293, 2005
  • Tachibana K, Suzuki K, Mori E, Miura N, Kawashima R, Horie K, Sato S, Tanji J, and Mushiake H. Neural Activity in the Human Brain Signals Logical Rule Identification. Journal of Neurophysiol 102:1526-1537, 2009
  • BabaT, Kikuchi A, Hirayama K, Nishio Y, Hosokai Y, Kanno S, Hasegawa T, Sugeno N, Konno M, Suzuki K, Takahashi S, Fukuda H, Aoki M, Itoyama Y, Mori E, Takeda A. Severe olfactory dysfunction is a prodromal symptom of dementia associated with Parkinson’s disease: a 3-year longitudinal study. Brain 135:161-169, 2012
  • Tanji K, Iwasaki M, Nakasato N, Suzuki K. Face specific broadband electrocorticographic spectral power change in the rhinal cortex. Neuroscience Letter 515:66-70, 2012
  • Sawada Y, NIshio Y, Suzuki K, Hirayama K, Takeda A, Hosokai Y, Ishioka T, Itoyama Y, Takahashi S, Fukuda H, Mori E. Attentional set-shifting deficit in Parkinson’s disease is associated with prefrontal dysfunction: an FDG-PET study. PLoS One 7:e38498, 2012
  • Tanji K, Sakurada K, Funiu H, Matsuda K, Kayama T, Suzuki K. Functional significance of the electrocorticographic auditory responses in the premotor cortex. Frontiers in Neuroscience 9: 78, Doi:10.3389/fnins.2015.00078, 2015

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Neural decoding of food preference and tendency for eating disorder

photo:Shinsuke Suzuki
Project leader

Frontier Research Institute for Interdisciplinary Sciences, Tohoku University
Assistant Professor Shinsuke Suzuki

Further information

Message from Project leader

You are what you eat. Food preference is a fundamental component of the decision-making process that all humans complete on a daily basis. A dysfunctional food preference may play a large role in the development of obesity and eating disorders. In this study, employing a new neuroimaging method known as ‘neural decoding’ that combines functional MRI with machine learning, we aim to (1) elucidate neural mechanisms underlying individual differences in food preference and to (2) build neural models that predict an individual’s food preference and tendency for eating disorder. We believe our study can provide significant insight into the neural underpinnings of food preference and potentially contributes to developing neuro-markers of eating disorders.

  • Project leader
    Assistant ProfessorShinsuke Suzuki

    Frontier Research Institute for Interdisciplinary Sciences, Tohoku University

    Research Area:
    Social Neuroscience, Neuroeconomics

    E-mail:
    shinsuke.szk*gmail.com
    (Please convert "*" into "@".)

    URL:
    https://sites.google.com/site/shinsukesuzuki0927/home

Selected Publication
  • Shinsuke Suzuki, Emily L. S. Jensen, Peter Bossaerts, John P. O’Doherty, "Behavioral contagion during learning about another agent's risk-preferences acts on the neural representation of decision risk", Proceedings of the National Academy of Sciences of the United States of America (PNAS), Vol.113, pp. 3755-3760, 2016.
  • Shinsuke Suzuki, Ryo Adachi, Simon Dunne, Peter Bossaerts, John P. O’Doherty, "Neural mechanisms underlying human consensus decision-making", Neuron, Vol. 86, pp. 591-602, 2015.
  • Hideyuki Takahashi, Kazunori Terada, Tomoyo Morita, Shinsuke Suzuki, Tomoki Haji, Hideki Kojima, Masahiro Yoshikawa, Yoshio Matsumoto, Takashi Omori, Minoru Asada, Eiichi Naito, "Different impressions of other agents obtained through social interaction uniquely modulate dorsal and ventral pathway activities in the social human brain", Cortex, Vol. 58, pp. 289-300, 2014.
  • Shinsuke Suzuki and Hiromichi Kimura, "Indirect reciprocity is sensitive to costs of information transfer", Scientific Reports, Vol. 3, No. 1435, 2013.
  • Shinsuke Suzuki, Norihiro Harasawa, Kenichi Ueno, Justin L Gardner, Noritaka Ichinohe, Masahiko Haruno, Kang Cheng, Hiroyuki Nakahara, "Learning to simulate other's decisions", Neuron, Vol. 74, No. 6, pp. 1125-1137, 2012.
  • Shinsuke Suzuki, Kazuhisa Niki, Syoken Fujisaki and Eizo Akiyama, “Neural basis of conditional cooperation”, Social Cognitive and Affective Neuroscience, Vol. 6, No. 3, pp. 338-347, 2011.
  • Shinsuke Suzuki and Hiromichi Kimura, "Oscillatory dynamics in the coevolution of cooperation and mobility", Journal of Theoretical Biology, Vol. 287, No. 1, pp. 42-47, 2011.
  • Shinsuke Suzuki and Eizo Akiyama, "Evolutionary stability of first-order-information indirect reciprocity in sizable groups", Theoretical Population Biology, Vol. 73, No. 3, pp. 426-436, 2008.
  • Shinsuke Suzuki and Eizo Akiyama, "Evolution of indirect reciprocity in groups of various sizes and comparison with direct reciprocity", Journal of Theoretical Biology, Vol. 245, No. 3, pp. 539-552, 2007.
  • Shinsuke Suzuki and Eizo Akiyama, "Reputation and the Evolution of Cooperation in Sizable Groups", Proceedings of the Royal Society B: Biological Sciences, Vol. 272, No. 1570, pp. 1373-1377, 2005.

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Developing fNIRS-based neuro-coginitive paradigms to realize early diagnosis and assessment of ADHD children

photo:Ippeita Dan
Project leader

Faculty of Science and Engineering, Chuo University
Professor Ippeita Dan

Further information

Message from Project leader

Attention-deficit hyperactivity disorder (ADHD) involves various behavioral characteristics. In some context, they may be regarded as behavioral symptoms, in others, whereas they may be viewed as individual personality. In order to facilitate the latter chance, the most important issue is to realize early diagnosis and treatment of ADHD to reduce harmful behaviors as early as at the age of six from which drug treatment is applicable. Thus far, we have revealed that the right prefrontal activation during inhibition and attention tasks can serve as an effective neurobiomarker to distinguish ADHD and typically-developing children and assess neuropharmachological effects of drug treatment of ADHD. Based on these achievement, we further aim to develop novel neurocognitive tasks to realize more robust fNIRS-based assessment of neurocognitive functions of ADHD children. Currently, we employ authentic go/nogo tasks and odd ball tasks to assess inhibition and attention functions of participants, but they are not fully optimized for children’s use, and sometimes are regarded as boring. For optimizing the tasks to children’s use, the key strategy is to introduce an element of gamification to arouse a feeling of curiosity among participants, and realize neurocognitive tasks that are easier to perform. This will realize earlier diagnosis and treatment of ADHD children and thereby lead to promote their quality-of-lives.

  • Project leader
    ProfessorIppeita Dan

    Faculty of Science and Engineering, Chuo University

    Research Area:
    Cognitive neurosciences, Psychometrics

    E-mail:
    dan*brain-lab.jp
    (Please convert "*" into "@".)

    URL:
    http://brain-lab.jp/

Selected Publication
  • Monden Y, Dan I, Nagashima M, Dan H, Uga M, Ikeda T, Tsuzuki D, Kyutoku Y, Gunji Y, Hirano D, Taniguchi T, Shimoizumi H, Watanabe E, Yamagata T: Individual classification of ADHD children by right prefrontal hemodynamic responses during a go/no-go task as assessed by fNIRS. NeuroImage: Clin., 9, 1-12, 2015
  • Nagashima M, Monden Y, Dan I, Dan H, Mizutani T, Tsuzuki D, Kyutoku Y, Gunji Y, Hirano D, Taniguchi T, Shimoizumi H, Momoi MY, Yamagata T, Watanabe E.: Neuropharmacological effect of atomoxetine on attention network in children with attention deficit hyperactivity disorder during oddball paradigms as assessed using functional near-infrared spectroscopy. Nurophotonics, 1, 025007., 2014
  • Nagashima M, Monden Y, Dan I, Dan H, Tsuzuki D, Mizutani T, Kyutoku Y, Gunji Y, Momoi MY, Watanabe E, Yamagata T.: Neuropharmacological effect of methylphenidate on attention network in children with attention deficit hyperactivity disorder during oddball paradigms as assessed using functional near-infrared spectroscopy. Nurophotonics, 1, 015001., 2014
  • Nagashima M, Monden Y, Dan I, Dan H, Tsuzuki D, Mizutani T, Kyutoku Y, Gunji Y, Hirano D, Taniguchi T, Shimoizumi H, Momoi MY, Watanabe E, Yamagata T.: Acute neuropharmacological effects of atomoxetine on inhibitory control in ADHD children: A fNIRS study. NuroImage:Clinical, 6, 192-201, 2014
  • Tsuzuki D, Dan I,: Spatial registration for functional near-infrared spectroscopy: from channel position on the scalp to cortical location in individual and group analyses. NeuroImage, 85, 92-103, 2014
  • Monden Y, Dan H, Nagashima M, Dan I, Tsuzuki D, Kyutoku Y, Gunji Y, Yamagata T, Watanabe E, Momoi MY: Right prefrontal activation as a neuro-functional biomarker for monitoring acute effects of methylphenidate in ADHD children: An fNIRS study. NuroImage:Clinical, 1, 131-140, 2012
  • Tsuzuki D, Jurcak V, Singh AK, Okamoto M, Watanabe E, Dan I: Virtual spatial registration of stand-alone functional NIRS data to MNI space. NeuroImage, 34, 1506-1518, 2007
  • Jurcak V, Tsuzuki D, Dan I: 10/20, 10/10 and 10/5 systems revisited: their validity as relative head-surface-based positioning systems. NeuroImage, 34, 1600-1611, 2007
  • Singh A, Okamoto M, Dan H, Jurcak V, Dan I: Spatial registration of multichannel multi-subject fNIRS data to MNI space without MRI. NeuroImage, 27, 842-851, 2005
  • Okamoto M, Dan H, Sakamoto K, Takeo K, Shimizu K, Kohno S, Oda I, Isobe S, Suzuki T, Kohyama K, Dan I: Three-dimensional probabilistic anatomical cranio-cerebral correlation via the international 10-20 system oriented for transcranial functional brain mapping. NeuroImage, 21, 99-111, 2004

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Neural mechanisms underlying the individual differences of human memories modulated by social trait and aging

photo:Takashi Tsukiura
Project leader

Department of Cognitive and Behavioral Sciences, Graduate School of Human and Environmental Studies, Kyoto University
Professor Takashi Tsukiura

Further information

Message from Project leader

Individual differences of human memory functions are often observed in our daily lives. However, little is known about the neural mechanisms underlying the individual differences in episodic memories. Our projects tackle this issue by fMRI technique for healthy young and older adults. In our fMRI studies, we particularly focus on individual differences of social trait and aging as factors to affect memory functions, and investigate how memory-related activation is modulated by these factors. To examine the effects of social trait on individual memory abilities, we conduct multiple fMRI studies to find memory-related activation modulated by empathy- and competition-related traits in social interactions with others. In studies of aging and memory, we focus on age-related difference of activation during the processing of "destination memory", which is one of the new concepts in human memories and is defined as the ability to remember the destination to whom a piece of information was addressed. To identify the neural mechanisms associated with an interaction between destination memory and aging, we scan healthy young and older adults during the encoding and/or retrieval of destination memories. The findings of these studies could provide a potential framework to understand individual differences of human cognitive functions in a social context.

  • Project leader
    ProfessorTakashi Tsukiura

    Department of Cognitive and Behavioral Sciences, Graduate School of Human and Environmental Studies, Kyoto University

    Research Area:
    Cognitive Neuroscience, Neuropshychology

    E-mail:
    tsukiura.takashi.6c*kyoto-u.ac.jp
    (Please convert "*" into "@".)

    URL:
    http://www.memory.jinkan.kyoto-u.ac.jp/index-e.html

Selected Publication
  • Shigemune Y., Tsukiura T., Nouchi R., Kambara T., Kawashima R. Neural mechanisms underlying the reward-related enhancement of motivation when remembering episodic memories with high difficulty. Human Brain Mapping, in press
  • Kaneda T., Shigemune Y., Tsukiura T. Lateral and medial prefrontal contributions to emotion generation by semantic elaboration during episodic encoding. Cognitive, Affective, and Behavioral Neuroscience, 17, 143-157, 2017
  • Sugimoto H., Shigemune Y., Tsukiura T. Competing against a familiar friend: Interactive mechanism of the temporo-parietal junction with the reward-related regions during episodic encoding. Neuroimage, 130, 261-272, 2016
  • Shingaki H., Park P., Ueda K., Murai T., Tsukiura T. Disturbance of time orientation, attention and verbal memory in amnesic patients with confabulation. Journal of Clinical and Experimental Neuropsychology, 38, 171-182, 2016
  • Shigemune Y., Tsukiura T., Kambara T., Kawashima R. Remembering with gains and losses: Effects of monetary rewards and punishments on successful encoding activation of source memories. Cerebral Cortex, 24, 1319-1331, 2014
  • Takada A., Park P., Shigemune Y., Tsukiura T. Health-related QOL and lifestyles are associated with cognitive functions in elderly people, Psychologia, 57, 177-200, 2014
  • Tsukiura T., Shigemune Y., Nouchi R., Kambara T., Kawashima R. Insular and hippocampal contributions to remembering people with an impression of bad personality, Social Cognitive and Affective Neuroscience, 8, 515-522, 2013
  • Tsukiura T., Cabeza R. Remembering beauty: Roles of orbitofrontal and hippocampal regions in successful memory encoding of attractive faces, Neuroimage, 54, 653-660, 2011
  • Tsukiura T., Sekiguchi A., Yomogida Y., Nakagawa S., Shigemune Y., Kambara T., Akitsuki Y., Taki Y., Kawashima R. Effects of aging on hippocampal and anterior temporal activations during successful retrieval of memory for face-name associations, Journal of Cognitive Neuroscience, 23, 200-213, 201
  • Tsukiura T., Cabeza R. Shared brain activity for aesthetic and moral judgments: implications for the Beauty-is-Good stereotype, Social Cognitive and Affective Neuroscience, 6, 138-148, 2011

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Quantitative understanding of brain individuality by visualizing semantic representation in twins

photo:Shunsuke Toyoda
Project leader

Center for Twin Research, Graduate School of Medicine, Osaka University
Visiting Researcher Shunsuke Toyoda

Further information

Message from Project leader

The brain is a foundation for creating high-level information processing, but little is known about how the individual differences are influenced by genetic and environmental factors. In this study, we quantify and visualize semantic representation of natural audiovisual experiences in the twin brains by functional magnetic resonance imaging (fMRI) and model-based analysis. In addition, by integrating information such as personality, genomic and epigenomic information and epidemiological data, we try to quantitatively understand genetic and environmental factors that contribute unique perceptual and cognitive functions.

  • Project leader
    Visiting ResearcherShunsuke Toyoda

    Center for Twin Research, Graduate School of Medicine, Osaka University

    Research Area:
    Neuroscience, Molecular biology

    E-mail:
    toyoda*twin.med.osaka-u.ac.jp
    (Please convert "*" into "@".)

Selected Publication
  • Tarusawa E, Sanbo M, Okayama A, Miyashita T, Kitsukawa T, Hirayama T, Hirabayashi T, Hasegawa S, Kaneko R, Toyoda S, Kobayashi T, Kato-Itoh M, Nakauchi H, Hirabayashi M, Yagi T, Yoshimura Y: Establishment of high reciprocal connectivity between clonal cortical neurons is regulated by the Dnmt3b DNA methyltransferase and clustered protocadherins. BMC biology, 14, 103, 2016
  • Toyoda S, Kawaguchi M, Kobayashi T, Tarusawa E, Toyama T, Okano M, Oda M, Nakauchi H, Yoshimura Y, Sanbo M, Hirabayashi M, Hirayama T, Hirabayashi T, Yagi T: Developmental epigenetic modification regulates stochastic expression of clustered protocadherin genes, generating single neuron diversity. Neuron, 82, 94-108, 2014
  • Yokota S, Hirayama T, Hirano K, Kaneko R, Toyoda S, Kawamura Y, Hirabayashi M, Hirabayashi T, Yagi T: Identification of the cluster control region for the protocadherin-beta genes located beyond the protocadherin-gamma cluster. The Journal of biological chemistry, 286, 31885-31895, 2011

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An integrative study of individual differences derived from color vision polymorphisms

photo:Chihiro Hiramatsu
Project leader

Department of Human Science, Faculty of Design, Kyushu University
assistant professor Chihiro Hiramatsu

Further information

Message from Project leader

Large color vision variations originating from genetic polymorphisms have been identified in humans. Most humans have trichromatic vision, which compares the signaling from cone photoreceptors of three classes that absorb different parts of the visible light spectrum. However, approximately 5 - 8 % of men experience dichromatic vision based on the comparison of output of cone photoreceptors of two classes, or trichromatic vision, wherein perception is similar to that dichromatic vision. Despite advances in understanding differences in perceiving simple colors among color vision types, limited information is available on the influence of color vision differences at the behavioral and cognitive levels. Our group aims to elucidate how color vision variations influence gaze patterns towards complex images and how they lead to differences in the impressions of these images. As genetic and perceptual differences in color vision are clearly related, color vision variations serve as excellent models to comprehensively investigate individual differences by attempting their integration at the genetic, behavioral, and cognitive level.

image
  • Project leader
    assistant professorChihiro Hiramatsu

    Department of Human Science, Faculty of Design, Kyushu University

    Research Area:
    Vision science

    E-mail:
    chihiro*design.kyushu-u.ac.jp
    (Please convert "*" into "@".)

    URL:
    http://www.design.kyushu-u.ac.jp/~divsense/

Selected Publication
  • Hiramatsu C, Melin AD, Aureli F, Schaffner CM, Vorobyev M, Matsumoto Y, Kawamura S: Importance of achromatic contrast in short-range fruit foraging of primates. PLoS One, 3, 10, e3356, 2008
  • Hiramatsu C, Melin AD, Aureli F, Schaffner CM, Vorobyev M, Kawamura S: Interplay of olfaction and vision in fruit foraging of spider monkeys. Animal Behaviour, 77, 1421-1426, 2009
  • Hiramatsu C, Goda N, Komatsu H: Transformation from image-based to perceptual representation of materials along the human ventral visual pathway. Neuroimage, 57, 482-494, 2011
  • Hiramatsu C, Fujita K, Visual categorization of surface qualities of materials by capuchin monkeys and humans. Vision Research, 115, 71-82, 2015

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Elucidation of cognitive and neural bases of individualities related to specialties and difficulties in daily life of people with developmental disorders

photo:Makoto Wada
Project leader

Department of Rehabilitation for Brain Functions, Research Institute of National Rehabilitation Center for Persons with Disabilities
Section Chief of Developmental Disorders Section Makoto Wada

Further information

Message from Project leader

We aim to elucidate cognitive neural bases of individualities that are related to specialties and difficulties in daily life of people with developmental disorders. To date, it has been gradually found that impairments in sensory-motor processing and body representations in individuals with autism spectrum disorder (ASD) cause severe declines in quality of life. We found distinctive features in such functions of individuals with ASD by using several psychophysical studies dealing with sensory-motor processing. However, we also found that there were wide ranges of individuality in the task results. Diversities in neural systems may cause such individualities. In the present study, we aim to elucidate relationships between such cognitive neural bases and individualities of daily life by conducting several psychophysical experiments, psychological tests and interviews. Ultimate purpose of our study is to support making a convivial society for peoples with and without developmental disorders by developing new support methods and promoting understanding individuality of developmental disorders.

  • Project leader
    Section Chief of Developmental Disorders SectionMakoto Wada

    Department of Rehabilitation for Brain Functions, Research Institute of National Rehabilitation Center for Persons with Disabilities

    Research Area:
    Cognitive science, Neurophysiology

    E-mail:
    wada-makoto*rehab.go.jp
    (Please convert "*" into "@".)

    URL:
    http://www.rehab.go.jp/ri/noukinou/hattatsu/index_eng.html

Selected Publication
  • Ide M, Wada M: Salivary oxytocin concentration associates with the subjective feeling of body ownership during the rubber hand illusion. Frontiers in Human Neuroscience, 11, 166, 2017.
  • Wada M, Takano K, Ora H, Ide M, Kansaku K: The Rubber Tail Illusion as Evidence of Body Ownership in Mice. Journal of Neuroscience, 36, 11133-11137, 2016.
  • Ide M, Hidaka S, Ikeda H, Wada M: Neural mechanisms underlying touch-induced visual perceptual suppression: An fMRI study. Scientific Reports, 6, 37301, 2016.
  • Ide M, Wada M: Periodic visuotactile stimulation slowly enhances the rubber hand illusion in individuals with high autistic traits. Frontiers in Integrative Neuroscience, 10, 21, 2016.
  • Wada M, Ide M: Rubber hand presentation modulates visuotactile interference effect, especially in persons with high autistic traits. Experimental Brain Research, 234, 51-65, 2016.
  • Nishikawa N, Shimo Y, Wada M, Hattori N, Kitazawa S: Effects of aging and idiopathic Parkinson’s disease on tactile temporal order judgment. PLoS One, 10, e0118331, 2015.
  • Wada M, Suzuki M, Takaki A, Miyao M, Spence C, Kansaku K: Spatio-temporal processing of tactile stimuli in autistic children. Scientific Reports, 4, 5985, 2014.
  • Takahashi T, Kansaku K, Wada M, Shibuya S, Kitazawa S: Neural Correlates of Tactile Temporal-Order Judgment in Humans: an fMRI Study. Cereb Cortex, 23, 1952-1964, 2013.
  • Wada M, Takano K, Ikegami S, Ora H, Spence C, Kansaku K: Spatio-temporal updating in the left posterior parietal cortex. PLoS One,7, e39800, 2012.
  • Wada M, Watanabe S, Chung U, Higo N, Taniguchi T, Kitazawa S: Noninvasive bioluminescence imaging of c-fos expression in the mouse barrel cortex. Behavioural Brain Research, 208, 158-162, 2010.
  • Wada M, Higo N, Moizumi S, Kitazawa S: c-Fos expression during temporal order judgment in mice. PLoS One, 5,e10483, 2010.

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A02: Fundamental research on generative brain systems for animal individuality

Exploring novel molecular mechanisms underlying learning, memory and cognition.

photo:Natsumi Ageta-Ishihara
Project leader

Graduate School of Science, Nagoya University
Lecturer Natsumi Ageta-Ishihara

Further information

Message from Project leader

Septin filaments are polymers of GTP-binding proteins abundant in neurons. Previous studies revealed that septin is required for neurite outgrowth, besides their implications in mammalian neuronal migration, spine morphogenesis, synaptic transmission, and neuropsychiatric disorders. In most cases, the detailed molecular mechanism is unknown. We reported that septins provide a physical scaffold for HDAC6 to achieve efficient microtubule deacetylation, thereby negatively regulating microtubule stability to an optimal level for neuritogenesis (Nature Commun 2013) and CDC42EP4/septin-based glial scaffold facilitates perisynaptic localization of GLAST and optimizes the efficiency of glutamate-buffering and clearance (Nature Commun 2015). However, mice that lack one or two septin genes are largely normal, due partly to redundancy and adaptive compensations. For sensitive, unbiased detection of neural phenotypes of those mutants, we have conducted behavioral screening. We observed that specific cognitive abilities are impaired in these mice. The unique line may provide a clue to unknown molecular mechanisms underlying learning, memory and cognition.

  • Project leader
    LecturerNatsumi Ageta-Ishihara

    Graduate School of Science, Nagoya University

    Research Area:
    Neurochemistry

    E-mail:
    ageta-ishihara.natsumi*h.mbox.nagoya-u.ac.jp
    (Please convert "*" into "@".)

    URL:
    https://sites.google.com/site/kinoshitalabnagoya/

Selected Publication
  • Parajuli L, Ageta-Ishihara N, Ageta H, Fukazawa Y, Kinoshita M: Methods for Immunoblot Detection and High-resolution Subcellular Mapping of Septin. Methods in Cell Biology, Septins, 136, Chapter 16, 2016
  • Horigane S*, Ageta-Ishihara N*(*equal contribution), Kamijo S, Fujii H, Okamura M, Kinoshita M, Takemoto-Kimura S, Bito H: Facilitation of axon outgrowth via a Wnt5a-CaMKK-CaMKI pathway during neuronal polarization.Molecular brain, 9(1), 8, 2016
  • Ageta-Ishihara N, Yamazaki M, Konno K, Nakayama H, Abe M, Hashimoto K, Nishioka T, Kaibuchi K, Hattori S, Miyakawa T, Tanaka K, Huda F, Hirai H, Hashimoto K, Watanabe M, Sakimura K, Kinoshita M: A CDC42EP4/septin-based perisynaptic glial scaffold facilitates glutamate clearance. Nature Communications, 6, 10090, 2015
  • Kitao Y, Ageta-Ishihara N, Takahashi R, Kinoshita M, Hori O: Transgenic supplementation of SIRT1 fails to alleviate acute loss of nigrostriatal dopamine neurons and gliosis in a mouse model of MPTP-induced parkinsonism. F1000Research, 4, 130, 2015
  • Watanabe S*, Ageta-Ishihara N*(*equal contribution), Nagatsu S*, Takao K, Komine O, Endo F, Miyakawa T, Misawa H, Takahashi R, Kinoshita M, Yamanaka K: SIRT1 overexpression ameliorates a mouse model of SOD1-linked amyotrophic lateral sclerosis via HSF1/HSP70i chaperone system.Molecular brain, 7, 62, 2014
  • Ageta-Ishihara N, Miyata T, Ohshima C, Watanabe M, Sato Y, Hamamura Y, Higashiyama T, MazitschekR, Bito H, Kinoshita M: Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation.Nature Communications, 4, 2532, 2013
  • Ageta-Ishihara N, Yamakado H, Morita T, Hattori S, Takao K, Miyakawa T, Takahashi R, Kinoshita M: Chronic overload of SEPT4, a parkin substrate that aggregates in Parkinson's disease, causes behavioral alterations but not neurodegeneration in mice.Molecular brain, 6, 35, 2013
  • Ageta-Ishihara N, Takemoto-Kimura S, Nonaka M, Adachi-Morishima A, Suzuki K, KamijoS, Fujii H, Mano T, Blaeser F, Chatila TA, Mizuno H, Hirano T, Tagawa Y, Okuno H, Bito H: Control of cortical axon elongation by a GABA-driven Ca2+/calmodulin-dependent protein kinase
    Cascade. Journal of Neuroscience, 29, 13720-13729, 2009

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Investigation of the link between individual differences in stress response and the styles of reward-based decision making

photo:IGUCHI, Yoshio
Project leader

Department of Molecular Genetics Institute of Biomedical Sciences, Fukushima Medical University
Assistant Professor IGUCHI, Yoshio

Further information

Message from Project leader

Life is a series of operant choices (decision making) governed by two forms of action control: 1) goal-directed processes (deliberative and slow), based on prediction and evaluation of the outcomes of action and 2) habit processes (reflecting and rapid), which do not use the prediction and evaluation. A well-balanced combination of the two processes corresponding to each learning stage is essential for a sound daily life; however, it can be disrupted by various types of stress, a risk factor for psychiatric disorders. However, given the individual differences in stress responses (i.e., vulnerability and resilience), it may be reasonable that possible physiological styles in decision making, varying across the goal-directed-habit spectrum, correlate with individual differences in stress responses. Here, we test the hypothesis that the functional characteristics of the locus coeruleus noradrenergic projection to the medial prefrontal cortex, which has been implicated in both decision making and stress response, manifest as individual differences in decision-making style and stress response. Toward this aim, we employ a combination of several methods, including behavioral tasks developed in experimental psychology, biochemical assays, and manipulation of neuronal activity with molecular genetic tools. The results could contribute to protection against psychiatric disorders and optimization of therapeutic strategies.

  • Project leader
    Assistant ProfessorIGUCHI, Yoshio

    Department of Molecular Genetics Institute of Biomedical Sciences, Fukushima Medical University

    Research Area:
    Behavioral Neuroscience, Experimental Psychology

    E-mail:
    yiguchi*fmu.ac.jp
    (Please convert "*" into "@".)

    URL:
    http://www.fmu.ac.jp/home/molgenet/en/

Selected Publication
  • Iguchi Y, Lin Z, Nishikawa H, Minabe Y, Toda S: Identification of an unconventional process of instrumental learning characteristically initiated with outcome devaluation-insensitivity and generalized action selection. Scientific Reports, 7:43307, 2017
  • Toda S, Iguchi Y, Lin Z, Nishikawa H, Nagasawa T, Watanabe H, Minabe Y: Reconsidering animal models of major depressive disorder in the elderly. Frontiers in Aging Neuroscience, 8: 188, 2016
  • Iguchi Y, Kosugi S, Lin Z, Nishikawa H, Minabe Y, Toda S: Pre-stress performance in an instrumental training predicts post-stress behavioral alterations in chronically stressed rats. Frontiers in Behavioral Neuroscience, 9: 119, 2015
  • Iguchi Y, Kosugi S, Nishikawa H, Lin Z, Minabe Y, Toda S: Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions. PLoS ONE, 9(12):e114024, 2014
  • Iguchi Y: Role of incentive learning in reduction of instrumental performance in rats (Rattus norvegicus) by irrelevant drive state. Japanese Journal of Animal Psychology, 64, 11-18, 2014
  • Iguchi Y, Fukumoto K, Sawa K, Ishii K: Effects of extended context discrimination training and context extinction on transfer of context dependency of conditioned flavor aversion. Behavioural Processes, 103, 218-227, 2014
  • Iguchi Y, Sawa K, Ishii K: Learning about absent outcome in the presence of conditioned excitor and inhibitor: A conditioned flavor preference study. International Journal of Comparative Psychology, 23, 121-144, 2010

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Social and epigenetic factors underpinning ant behavioral variability.

photo:Yasukazu Okada
Project leader

Laboratory of Animal Ecology, Department of Biological Sciences
School of Science, Tokyo Metropolitan University (TMU), JAPAN.
Associate Professor Yasukazu Okada

Further information

Message from Project leader

Social interactions such as parent-child interaction and sexual interaction, have fundamental effects on the development of animal personality. As in group-living vertebrates, social insects such as ants and bees often develop behavioral variation based on social interactions. Interestingly, such behavioral variation are considered to be functional in colony-level activities. We focus on the behavioral variability of ants in this project. First, we quantify social interaction and behavioral variability among nest-mates using the automated behavioral tracking. Second, molecular basis of behavioral variation are analyzed by examining the brain gene expression patterns. We will try to integrate the ultimate and proximate factors and that generate the personality and social organization.

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  • Project leader
    Associate ProfessorYasukazu Okada

    Laboratory of Animal Ecology, Department of Biological Sciences
    School of Science, Tokyo Metropolitan University (TMU), JAPAN.

    Research Area:
    Ecologial developmental biology, ethology

    E-mail:
    okayasukazu*gmail.com
    (Please convert "*" into "@".)

    URL:
    https://purpleandorange.jimdo.com

Selected Publication
  • Social dominance alters nutrition-related gene expression immediately: transcriptomic evidence from a monomorphic queenless ant.
    Okada Y*, Watanabe Y, Mandy MYT, Tsuji K, Mikheyev AS*.
    Molecular Ecology in press
  • Ant circadian activity associated with brood care type Fujioka H, Abe MS, Fuchikawa T, Tsuji K, Shimada M, Okada Y*.
    Biology Letters (2017) 13: 20160743.
  • Queen contact and among-worker interactions dually suppress worker brain dopamine as a potential regulator of reproduction in an ant.
    Shimoji H*, Aonuma H, Miura T, Tsuji K, Sasaki K, Okada Y*.
    Behavioral Ecology and Sociobiology (2017) 71: 35.
  • Histone deacetylases control module-specific phenotypic plasticity in beetle weapons.
    Ozawa T, Mizuhara T, Arata M, Shimada M, Niimi T, Okada K, Okada Y*, Ohta K*.
    Proceedings of the National Academy of Sciences (2016) 113: 15042-15047.
  • Mutual intra- and interspecific social parasitism between parapatric sister species of Vespula wasps.
    Saga T*, Kanai M, Shimada M, Okada Y.
    Insectes Sociaux (2017) 64: 95
  • Social dominance and reproductive differentiation mediated by the dopaminergic signaling in a queenless ant.
    Okada Y*, Sasaki K, Miyazaki S, Shimoji H, Tsuji K, Miura T.
    Journal of Experimental Biology (2015) 218, 1091-1098
  • Morphological variability of intercastes in the ant Temnothorax nylanderi: pattern of trait expression and modularity.
    Okada Y, Plateaux L, Peeters C.
    Insectes Sociaux (2013) 60: 319-328
  • Ovarian development and insulin-signaling pathways during reproductive differentiation in the queenless ponerine ant Diacamma sp.
    Okada Y., Miyazaki S., Miyakawa H., Ishikawa A., Tsuji K., Miura T Journal of Insect Physiology (2010) 56, 288-295

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Neural mechanisms of interspecies affiliative relationships

photo:Shota OKABE
Project leader

Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University
Postdoctoral fellow Shota OKABE

Further information

Message from Project leader

Social animals can develop affiliative relationships with not only conspecific individuals but also heterospecific individuals. Wild animals that have been artificially nurtured and raised by humans are known to exhibit affiliative behavior toward their caregivers. Companion animals such as dogs and cats have adapted themselves to human society by developing affiliative relationships with humans. The development of heterospecific affinity can lead to the formation of a community composed of heterogeneous individuals. Thus, an understanding of the neural mechanisms of interspecific relationships may be shed light on the mechanisms underlying the diversified community.
In our preliminary study, rats that received stroking stimuli by human showed affiliative responses to human. Several brain regions showed positive correlations between their neural activity and affiliative behaviors. The aim of this study is to clarify the neural mechanisms for formation of affiliative relationships between humans and animals by making use of a rat-human affiliative model.

  • Project leader
    Postdoctoral fellowShota OKABE

    Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University

    Research Area:
    Ethology, Behavioral neuroscience

    E-mail:
    shota.okabe*jichi.ac.jp
    (Please convert "*" into "@".)

    URL:
    http://www.jichi.ac.jp/usr/pys1/admnpys1/

Selected Publication
  • Okabe S, Tsuneoka Y, Takahashi A, Ooyama R, Watarai A, Maeda S, Honda Y, Nagasawa M, Mogi K, Nishimori K, Kuroda M.
    Pup exposure facilitates retrieving behavior via the oxytocin neural system in female mice. Psychoneuroendocrinology, 79, 20-30. 2017.
  • 1Takahashi T, 1Okabe S, 1Broin P, 1Nishi A, Ye K, Beckert M, Izumi T, Machida A, Kang G, Abe S, Pena J L, Golden A, Kikusui T, Hiroi N.
    Structure and function of neonatal social communication in genetic mouse model of autism. Molecular Psychiatry, 21, 1208-1214. 2015. 1 Equal contribution.
  • Onaka T, Okabe S, Takayanagi Y, Yoshida M.
    Noxious or non-nocious inputs to oxytocin neurons: possible roles in the control of behaviors. Interdisciplinary Information Science, 21, 189-195. 2015.
  • Okabe S, Yoshida M, Takayanagi Y, Onaka T.
    Activation of hypothalamic oxytocin neurons following tactile stimuli in rats. Neuroscience Letter, 600, 22-27. 2015.
  • Okabe S, Kitano K, Nagasawa M, Mogi K, Kikusui T.
    Tesutosterone inhibits facilitating effects of parenting experience on parental behavior and the oxytocin neural system in mice. Physiology and Behavior, 118, 159-164. 2013.
  • Okabe S, Nagasawa M, Kihara T, Kato M, Harada T, Koshida N, Mogi K, Kikusui T.
    Pup odor and ultrasonic vocalizations synergistically stimulate maternal attention in mice. Behavioral Neuroscience, 127, 432-438. 2013.
  • Okabe S, Nagasawa M, Mogi K, Kikusui T.
    The importance of mother- infant communication for social bond formation in mammals. Animal Science Journal, 83, 446-452. 2012.
  • Okabe S, Nagasawa M, Kihara T, Kato M, Harada T, Koshida N, Mogi K, Kikusui T.
    The effects of social experience and gonadal hormones on retrieving behavior of mice and their responses to pup ultrasonic vocalizations. Zoological Science, 27, 790-795. 2010

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How to modulate individuality

photo:Ryosuke Kaneko
Project leader

Gunma University Graduate School of Medicine
Assistant Professor Ryosuke Kaneko

Further information

Message from Project leader

Individuality is created by molecules that are responsible for formation of specific neural circuits. We are focusing on clustered protocadherins (Pcdh) as a candidate for individuality creator. In this study, we are addressing following questions using fluorescent protein knock-in mice: (a) Quantification of Pcdh dynamism, (b) Analyzing relationship between Pcdh expression and neuronal connection, (c) Identifying underlying mechanism of Pcdh expression. These experiments will answer how to modulate individuality.

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Selected Publication
  • Hasegawa S, Kumagai M, Hagihara M, Nishimaru H, Hirano K, Kaneko R, Okayama A, Hirayama T, Sanbo M, Hirabayashi M, Watanabe M, Hirabayashi T, Yagi T: Distinct and Cooperative Functions for the Protocadherin-a, -b and –g Clusters in Neuronal Survival and Axon Targeting. Front Mol Neurosci. 9, 155, 2016
  • Tarusawa E, Sanbo M, Okayama A, Miyashita T, Kitsukawa T, Hirayama T, Hirabayashi T, Hasegawa S, Kaneko R,Toyoda S, Kobayashi T, Kato-Itoh M, Nakauchi H, Hirabayashi M, Yagi T, Yoshimura Y: Establishment of high reciprocal connectivity between clonal cortical neurons is regulated by the Dnmt3b DNA methyltransferase and clustered protocadherins. BMC Biology, 14, 103, 2016
  • Kaneko R, Sato A, Hamada S, Yagi T, Ohsawa I, Ohtsuki M, Kobayashi E, Hirabayashi M, Murakami T: Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT). Transgenic Research, 25, 413-424, 2016
  • Kaneko R, Abe M, Hirabayashi T, Uchimura A, Sakimura K, Yanagawa Y, Yagi T: Expansion of stochastic expression repertoire by tandem duplication in mouse Protocadherin-a cluster. Scientific Reports 4, 6263, 2014
  • Kaneko R, Kakinuma T, Sato A, Jinno-Oue A, Hata H: Littermate influence on infant growth in mice: Comparison of SJL/J and ICR as cotransferred carrier embryos. Experimental Animals, 63, 375-381, 2014
  • Hirano K, Kaneko R (co-first author), Izawa T, Kawaguchi M, Kitsukawa T, Yagi T: Single-neuron diversity generated by Protocadherin-β cluster in mouse central and peripheral nervous systems. Front Mol Neurosci. 5, 90, 2012
  • Shino M, Kaneko R (co-first author), Yanagawa Y, Kawaguchi Y, Saito Y: Electrophysiological characteristics of inhibitory neurons of the prepositus hypoglossi nucleus as analyzed in Venus-expressing transgenic rats. Neuroscience, 197, 89-98, 2011
  • Kaneko R, Kawaguchi M, Toyama T, Taguchi T, Yagi T: Expression levels of Protocadherin-α transcripts are decreased by nonsense-mediated mRNA decay with frameshift mutations and by high DNA methylation in their promoter regions. Gene, 430, 86-94, 2009
  • Esumi S, Kaneko R, Kawamura Y, Yagi T: Split single cell RT-PCR analysis of Purkinje cells. Nature Protocols, 1, 2143-2151, 2006
  • Kaneko R, Kato H, Kawamura Y, Esumi S, Hirayama T, Hirabayashi T, Yagi T: Allelic gene regulation of Pcdh-α and Pcdh-γ clusters involving both monoallelic and biallelic expression in single Purkinje cells. J. Biol. Chem., 281, 30551-30560, 2006

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Understanding mechanism by which personalities are determined and developed and the development of methods to detect personalities from the view of neural circuits controlling social behaviors.

photo:Satoshi Kida
Project leader

Department of Bioscience, Faculty of Life science, University of Tokyo
Professor Satoshi Kida

Further information

Message from Project leader

Social behaviors including social approach, interaction, and recognition/discrimination are important components to determine and develop personality in human as well as animals. Especially, social recognition memory is an essential and basic component of social behaviors to discriminate familiar and novel animals/humans. On the other hand, developmental disorders of brain such as autism show abnormal social behaviors. Therefore, analyzing neural circuits controlling social behaviors and social memory is important to understand mechanism for the development and determination of personality from the view of basis and clinical researches. Therefore, in this study, we will try to identify neural circuits controlling social behaviors including social memory and discrimination and understand how social behaviors are regulated by performing analyses of molecular and cellular cognition and in silico analyses of neural circuits. Furthermore, we will try to develop methods to detect and compare personality in human/animals from the view of social behaviors.

Selected Publication
  • Tanimizu, T., Kenney., J.W., Okano, E., K. Kadoma., K, Frankland., P.W., Kida, S. Functional connectivity of multiple brain regions required for the consolidation of social recognition memory. J. Neurosci., in press.
  • Ishikawa, R., Fukushima, H., Frankland, P.W., Kida, S. Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval eLife, 5: e17464, 2016. doi: 10.7554/eLife.17464.
  • Kida, S. & Kato, T. Microendophenotypes of psychiatric disorders -Phenotypes of psychiatric disorders at the level of molecular dynamics, synapses, neurons, and neural circuits-. Current Molecular Medicine. 15:111-118, 2015
  • Fukushima, H., Zhang, Y., Archbol, G., Ishikawa, R., Nader, K. Kida, S. Enhancement of fear memory by retrieval through reconsolidation. eLife, 3, e02736, 2014
  • Nomoto, M., Takeda, Y., Uchida, S., Mitsuda, K., Enomoto, H., Saito, K., Choi, T., Watabe, A.M., Kobayashi, S., Masushige, S., Manabe, T. & Kida, S. Dysfunction of the RAR/RXR signaling pathway in the forebrain impairs hippocampal memory and synaptic plasticity. Mol. Brain. 5, 8 (2012).
  • Suzuki, A., Fukushima, H., Mukawa, T., Toyoda, H., Wu, L-J., Zhao, M-G., Hui Xu, H., Shang, Y., Endoh, K., Iwamoto, Mamiya, N., Okano, E., Hasegawa, H., Mercaldo, V., Yue Zhang, Y., Maeda, R., Ohta, M., Josselyn, S.A., Zhuo, M., & Kida, S. Up-regulation of CREB-mediated transcription enhances both short- and long-term memory. J. Neurosci. 31, 8786-8802 (2011)
  • Mamiya, N., Fukushima, H., Suzuki, A., Matsuyama, Z., Homma, S., Frankland, P.W. & Kida, S. Brain region-specific gene expression activation required for reconsolidation and extinction of contextual fear memory. J. Neurosci. 29, 402-13 (2009)
  • Fukushima, H., Maeda, R., Suzuki, R., Suzuki, A., Nomoto, M., Toyoda, H., Wu, L.-J., Xu, H., Zhao, M.-G., Ueda, K., Kitamoto, K., Mamiya, N., Yoshida, T., Homma, S., Masushige, S., Zhuo, M. & Kida, S. Up-regulation of CaMKIV improves memory formation and rescues memory loss with aging. J. Neurosci. 28, 9910-19 (2008).
  • Suzuki, A., Josselyn S., Frankland P., Masushige, S., Silva, A.J. & Kida, S. Memory reconsolidation and extinction have distinct temporal and biochemical signatures. J. Neurosci., 24, 4787-4795 (2004)
  • Kida, S., Josselyn, S., Peña de Ortiz, S., Kogan, J., Masushige, S. & Silva, A.J. CREB required for the stability of new and reactivated fear memory. Nature Neurosci., 5, 348-355 (2002)

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Emergence of offspring’s individuality in various oxygen environments during pregnancy

photo:Daisuke Sakai
Project leader

Graduate School of Brain Science, Doshisha University
Research assistant professor Daisuke Sakai

Further information

Message from Project leader

In mammals including humans, fetuses develop and grow in the womb. Maternal lifestyle factors such as diet, medicine, and oxygen are delivered to fetuses through maternal-fetal circulation, and those factors directly impact on the development or the growth of fetuses. Recent studies demonstrated that oxygen acts as a signaling molecule and regulates neural progenitor cell differentiation in developing brain. In this study, we focus on the role of maternal oxygen environment for brain development of fetuses, and consequent cortical excitatory-inhibitory balance and behavioral pattern of offspring. We will elucidate the molecular mechanisms of the emergence of behavioral individuality.

  • Project leader
    Research assistant professorDaisuke Sakai

    Graduate School of Brain Science, Doshisha University

    Research Area:
    Developmental Biology, Cell Biology

    E-mail:
    dsakai*mail.doshisha.ac.jp
    (Please convert "*" into "@".)

Selected Publication
  • Daisuke Sakai, Jill Dixon, Annita Achilleos, Michael Dixon, and Paul A Trainor; Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation. Nature Communications. 7, 10328, 2016
  • Daisuke Sakai, and Paul A Trainor; Face off against ROS: Tcof1/Treacle safeguards neuroepithelial cells and progenitor neural crest cells from oxidative stress during craniofacial development. Development, Growth and Differentiation. 58(7), 577-585, 2016
  • Daisuke Sakai, and Paul A Trainor; Gene transfer techniques in whole embryo cultured post-implantation mouse embryos. Methods in Molecular Biology. 1092, 227-234, 2014
  • Daisuke Sakai, Jill Dixon, Michael Dixon, and Paul A Trainor; Mammalian neurogenesis requires Treacle-Plk1 for precise control of spindle orientation mitotic progression and maintenance of neural progenitor cells. PLoS Genetics. 8(3), e1002566, 2012
  • Yoshio Wakamatsu, Daisuke Sakai, Takashi Suzuki, and Noriko Osumi; FilaminB is required for the directed localization of cell-cell adhesion molecules in embryonic epithelial development. Developmental Dynamics. 240 (1), 149-161, 2011
  • Daisuke Sakai, and Paul A Trainor; Treacher Collins syndrome: Unmasking the role of Tcof1/treacle. The International Journal of Biochemistry and Cell Biology. 41, 1229-1232, 2009
  • Natalie C Jones, Megan L Lynn, Karin Gaudenz, Daisuke Sakai, Kazushi Aoto, Jean-Phillipe Rey, Earl F Glynn, Lacey Ellington, Chunying Du, Jill Dixon, Michael J Dixon, and Paul A Trainor; Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nature Medicine. 14 (2), 125-133, 2008
  • Takashi Suzuki, Daisuke Sakai, Noriko Osumi, Hiroshi Wada and Yoshio Wakamatsu; Sox genes regulate type 2 collagen expression in avian neural crest cells. Development, Growth and Differentiation. 48(8), 477-486., 2006
  • Daisuke Sakai, Takashi Suzuki, Noriko Osumi, and Yoshio Wakamatsu; Cooperative action of Sox9, Snail2 and PKA signaling in early neural crest development. Development 133(7), 1323-1333, 2006

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Visual experience-dependent formation of individual circuits

photo:Sayaka Sugiyama
Project leader

Graduate School of Medical and Dental Sciences, Niigata University
Associate Professor Sayaka Sugiyama

Further information

Message from Project leader

It is generally thought that learning how to play instruments and sports or speaking languages is much easier during childhood than in adulthood. The young brain experiences a unique window 'critical period' when neuronal circuitry is intensively remodeled by experience. Rewiring neuronal circuits causes functional changes capable of influencing relevant cognition that are sustained into adulthood. Understanding of mechanism of critical period will contribute to the field of experience-dependent formation of individual circuits and safety manipulation of plasticity for recovery from brain disorders.
Childhood experience also impacts vision. Imbalanced visual experience, for instance by closing one eye for a brief period, leads to a rapid shift of neuronal spiking response in favor of the open eye (ocular dominance plasticity). From mouse to man, the seemingly innocuous imbalance of experience causes a reduction of visual acuity through the closed eye (amblyopia) that is difficult to improve in adulthood beyond the critical period. Our studies demonstrate that a homeodomain transcription factor Otx2, well known for its role in embryonic head formation, regulates the critical period in the postnatal visual cortex. Thus, we perform genome-wide target analysis of Otx2 to reveal how cellular/molecular mechanisms control visual plasticity. Moreover, we analyze the possibility that experience-dependent transfer of this homeoprotein may participate in individual circuit formation across brain regions.

Selected Publication
  • Hou X., Yoshioka N., Tsukano H., Sakai A., Miyata S., Watanabe Y., Yanagawa Y., Sakimura K., Takeuchi K., Kitagawa H., Hensch TK., Shibuki K., Igarashi M*. and Sugiyama S*. Chondroitin sulfate is required for onset and offset of critical period plasticity in visual cortex. Sci.Rep. in press
  • Sakai A., Nakato R., Ling Y., Hou X., Hara N., Iijima T., Yanagawa Y., Kuwano R., Okuda S., Shirahige K. and Sugiyama S*. Genome-wide target analyses of Otx2 homeoprotein in postnatal cortex. Front.Neurosci. 11, 307, 2017
  • Nakahara K., Adachi K., Kawasaki K., Matsuo T., Sawahata H., Majima K., Takeda M., Sugiyama S., Nakata R., Iijima A., Tanigawa H., Suzuki T., Kamitani Y. and Hasegawa I. : Associative-memory representations emerge as shared spatial patterns of theta activity spanning the primate temporal cortex. Nat. Comm. 7, 11827, 2016
  • Hou X., Katahira T., Ohashi K., Mizuno K., Sugiyama S*. and Nakamura H*. : Coactosin accelerates cell dynamism by promoting actin polymerization. Dev. Biol. 379, 53-63, 2013
  • Beurdeley M., Spatazza J., Lee H.H.C., Sugiyama S., Bernard C., Di Nardo A.A., Hensch T.K. and Prochiantz A. : Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex. J.Neurosci. 32, 9429-9437, 2012
  • Sugiyama S., and Nakamura H. : Clonal and widespread gene transfer by proviral electroporation for analysis of brain laminar formation. Springer, Electroporation and Sonoporation in Developmental Biology, Chapter 12, 117-128, 2009
  • Sugiyama S*., Prochiantz A. and Hensch T.K*. : From brain formation to plasticity: insights on Otx2 homeoprotein. Dev. Growth Differ. 51, 369-377, 2009
  • Sugiyama S., Di Nardo A.A., Aizawa S., Matsuo I., Volovitch M., Prochiantz A. and Hensch T.K.: Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity. Cell 134, 508-520, 2008
  • Sugiyama S. and Nakamura H.: The role of Grg4 in tectal laminar formation. Development 130, 451-462, 2003
  • Sugiyama S*., Funahashi J. and Nakamura H.: Antagonizing activity of chick Grg4 against tectum-organizing activity. Dev. Biol. 221, 168-180, 2000

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Neural mechanism in modulation of personality by experience

photo:Yousuke Tsuneoka
Project leader

Faculty of Medicine, Toho University
assistant professor Yousuke Tsuneoka

Further information

Message from Project leader

“Personality” should be modulated by the experiences after its establishment. For example, social contacts with lovers may induce changes of our personality and feeding palatability correlate with the personality. In the rodent model, it has been known that the independent behavioral phenotypes are changed after sexual behavior and parental behavior. In addition, high fat diet modulates olfaction, sexual behavior, and anxiety. These suggests the possibility that the various behaviors which are not directly linked in their behavioral paradigm link each other in the central nervous system. We tackled the brain mechanisms involved in the modulation of personality, focusing on the epigenetic factor, histone deacetyl transferase (HDAC). HDAC 4 shows transcriptional regulation in the nervous system and its activity is depended on the activation of neurons via its phosphorylation. In our preliminary study, it was suggested that HDAC 4 involved in the feeding regulation. We hypothesized that the HDAC 4 is one of the interface of personality modulation by the social experiences and environmental change. In this study, we try to show the involvement of HDAC 4 in the personality modulation, using genetic modulation of HDAC4 and other epigenetic factors.

  • Project leader
    assistant professorYousuke Tsuneoka

    Faculty of Medicine, Toho University

    Research Area:
    Neuroanatomy, ethology

    E-mail:
    yousuke.tsuneoka*med.toho-u.ac.jp
    (Please convert "*" into "@".)

    URL:
    http://www.toho-u.ac.jp/med/lab/lab_morphology.html

Selected Publication
  • Tsuneoka Y, Tsukahara S, Yoshida S, Takase K, Oda S, Kuroda M, Funato H. Moxd1 is a marker for sexual dimorphism in the medial preoptic area, bed nucleus of the stria terminalis and medial amygdala. Frontiers in Neuroanatomy 11: 26. 2017
  • Okabe S, Tsuneoka Y, Takahashi A, Ooyama R, Watarai A, Maeda S, Honda Y, Nagasawa M, Mogi K, Nishimori K, Kuroda M, Koide T, Kikusui T. Pup exposure facilitates retrieving behavior via the oxytocin neural system in female mice. Psychoneuroendocrinology 79: 20-30. 2017
  • Takase K, Tsuneoka Y, Oda S, Kuroda M, Funato H. High-fat diet feeding alters olfactory-, social-, and reward-related behaviors of mice independent of obesity. Obesity, 24: 886-894. 2016
  • Tsuneoka Y, Tokita K, Yoshihara C, Amano T, Esposito G, Huang AJ, Yu LMY, Odaka Y, Shinozuka K, McHugh TJ & Kuroda KO. Distinct preoptic-BST nuclei dissociate paternal and infanticidal behavior in mice. The EMBO Journal, 34: 2652-2670. 2015
  • Tsuneoka Y. Regulation of the host workers’ oviposition by the social parasite ant Polyergus samurai. Zoological Science, 31(7): 407-413. 2014
  • Tsuneoka Y, Maruyama T, Yoshida S, Nishimori K, Kato T, Numan M & Kuroda KO. Functional, anatomical, and neurochemical differentiation of medial preoptic area subregions in relation to maternal behavior in the mouse. Journal of Comparative Neurology, 521 (7): 1633-1663. 2013

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Effect of olfactory inputs on emergence of individuality

photo:Hirofumi Nishizumi
Project leader

Department of Brain Function, School of Medical Sciences, University of Fukui
Associate Professor Hirofumi Nishizumi

Further information

Message from Project leader

In mammals, including the human, behaviors and emotional status are regulated by the quality decisions of sensory inputs. Innate decisions for survival are mostly instinctive and mediated by the hard-wired neural circuits, whereas, memory-based learnt decisions are made depending upon past experiences. Recently, our group found that olfactory circuits are not merely refined, but newly generated in an activity-dependent manner. If olfactory inputs are blocked in neonates, social responses to unfamiliar mice are impaired in adults, showing autistic-like behaviors. In contrast, exposure of the newborn to a particular odorant generates the imprinted odor-memory that induces curiosity responses in adults even to aversive odorants. In this project, we plan to identify neural circuits and responding cortical areas responsible for the olfactory imprinting. We will also examine which part of neural circuits and brain regions are impaired when high-dose sensory inputs are repeatedly introduced. Our studies will shed light on the neurodevelopmental disorders caused by unusual sensory inputs in human.

  • Project leader
    Associate ProfessorHirofumi Nishizumi

    Department of Brain Function, School of Medical Sciences, University of Fukui

    Research Area:
    Molecular Biology, Neuroscience

    E-mail:
    saijyu*u-fukui.ac.jp
    (Please convert "*" into "@".)

    URL:
    http://koujinou.med.lab.u-fukui.ac.jp/ja

Selected Publication
  • Nishizumi H, Sakano H: Developmental regulation of neural map formation in the mouse olfactory system. Dev. Neurobiol., 75, 594-607, 2015.
  • Nishizumi H, Sakano H: Decoding and deorphanizing an olfactory map. Nat. Neurosci., 18, 1432-1433, 2015.
  • Nakashima A, Takeuchi H, Imai T, Saito H, Kiyonari H, Abe T, Chen A, Weinstein LS, Yu CR, Storm DR, Nishizumi H, Sakano H: Agonist-independent GPCR activity regulates anterior-posterior targeting of olfactory sensory neurons. Cell, 154, 1314-1325, 2013.
  • Aoki M, Takeuchi H, Nakashima A, Nishizumi H, Sakano H: Possible roles of Robo1+ ensheathing cells in guiding dorsal-zone olfactory sensory neurons in mouse. Dev. Neurobiol., 73, 828-840, 2013.
  • Takaba H, Imai T, Miki S, Morishita Y, Miyashita A, Ishikawa N, Nishizumi H, Sakano H: A major allogenic leukocyte-antigen in the agnathan hagfish. Scientific Reports, 3, 1716, 2013.
  • Takahashi H, Yoshihara S, Nishizumi H, Tsuboi A: Neuropilin2 is required for the proper targeting of ventral glomeruli in the mouse olfactory bulb. Mol. Cell. Neurosci., 44, 233-245, 2010.
  • Kishishita N, Matsuno T, Takahashi Y, Takaba H, Nishizumi H, Nagawa F: Regulation of antigen-receptor gene assembly in hagfish. EMBO Rep., 11, 126-132, 2010.
  • Nishizumi H, Kumasaka K, Inoue N, Nakashima A, Sakano H: Deletion of the core-H region in mice abolishes the expression of three proximal odorant receptor genes in cis. Proc. Natl. Acad. Sci. USA., 104, 20067-20072, 2007.
  • Nagawa F, Kishishita N, Shimizu K, Hirose S, Miyoshi M, Nezu J, Nishimura T, Nishizumi H, Takahashi Y, Hashimoto S, Takeuchi M, Miyajima A, Takemori T, Otsuka AJ, Sakano H: Antigen-receptor genes of the agnathan lamprey are assembled by a process involving copy choice. Nat. Immunol., 8, 206-213, 2007.
  • Oka Y, Kobayakawa K, Nishizumi H, Miyamichi K, Hirose S, Tsuboi A, Sakano H: O-MACS, a novel member of the medium-chain acyl-CoA synthetase family, specifically expressed in the olfactory epithelium in a zone specific manner. Eur. J. Biochem. 270, 1995-2004, 2003.

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CHD8 haploinsufficiency results in autistic-like phenotypes in mice

photo:Masaaki Nishiyama
Project leader

Department of Histology and Cell Biology, Graduate School of Medical Sciences, Kanazawa University
Professor Masaaki Nishiyama

Further information

Message from Project leader

Autism spectrum disorder (ASD) comprises a range of neurodevelopmental disorders characterized by deficits in social interaction and communication as well as by restricted and repetitive behaviours. ASD has a strong genetic component with high heritability. Exome sequencing analysis has recently identified many de novo mutations in a variety of genes in individuals with ASD, with CHD8, a gene encoding a chromatin remodeler, being most frequently affected. Whether CHD8 mutation is causative for ASD and how it might establish ASD traits have remained unknown, however. Here we show that mice heterozygous for Chd8 mutations manifest ASD-like behavioural characteristics including increased anxiety, repetitive behaviour, and altered social behaviour. CHD8 haploinsufficiency did not result in prominent changes in the expression of a few specific genes but rather gave rise to small but global changes in gene expression in mouse brain reminiscent of those in the brain of human ASD patients. Gene set enrichment analysis (GSEA) revealed that neurodevelopment is delayed in the mutant mouse embryos. Furthermore, reduced expression of CHD8 is associated with abnormal activation of RE-1 silencing transcription factor (REST), which suppresses the transcription of many neuronal genes. REST activation was also observed in the human ASD brain, and CHD8 was found to physically interact with REST in mouse brain. Our results are thus consistent with the notion that CHD8 haploinsufficiency is a highly penetrant risk factor for ASD, with disease pathogenesis likely resulting from a delay in neurodevelopment.

  • Project leader
    ProfessorMasaaki Nishiyama

    Department of Histology and Cell Biology, Graduate School of Medical Sciences, Kanazawa University

    Research Area:
    Epigenetics, Autism

    E-mail:
    nishiyam*staff.kanazawa-u.ac.jp
    (Please convert "*" into "@".)

Selected Publication
  • Katayama Y, *Nishiyama M, Shoji H, Ohkawa Y, Kawamura A, Sato T, Suyama M, Takumi T, Miyakawa T, *Nakayama KI (*Corresponding authors): CHD8 haploinsufficiency results in autistic-like phenotypes in mice. Nature, 537, 675-679, 2016.
  • Nishiyama M, Oshikawa K, Tsukada Y, Nakagawa T, Iemura S, Natsume T, Fan Y, Kikuchi A, Skoultchi AI, Nakayama KI: CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis. Nature Cell Biol., 11, 172-182, 2009.
  • Moroishi T, Nishiyama M, Takeda Y, Iwai K, Nakayama KI: The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo. Cell Metab., 14, 339-351, 2011.
  • Muto Y, *Nishiyama M, Nita A, Moroishi T, *Nakayama KI (*Corresponding authors): Essential role of FBXL5-mediated cellular iron homeostasis in maintenance of hematopoietic stem cells. Nature Commun., in press.
  • Nishiyama M, Skoultchi AI, Nakayama KI: Histone H1 recruitment by CHD8 is essential for suppression of the Wnt-beta-catenin signaling pathway. Mol. Cell. Biol., 32, 501-512, 2012.
  • Nishiyama M, Nakayama K, Tsunematsu R, Tsukiyama T, Kikuchi A, Nakayama KI: Early embryonic death in mice lacking the beta-catenin-binding protein Duplin. Mol. Cell. Biol., 24, 8386-8394, 2004.

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Molecular and cellular signatures for the memory update through the novelty recognition mechanisms

photo:Hotaka Fukushima
Project leader

Department of Bioscience, Faculty of Life Sciences, Tokyo University of Agriculture
Assistant Professor Hotaka Fukushima

Further information

Message from Project leader

When we recognize human or object, we retrieve memory and distinguish between known and unknown. Then we add new information to the original memory, or form a new memory. Sociability is formed by the memory update through such novelty recognition mechanisms, and personality is shown. Recent studies have shown that reactivated memory becomes labile through proteasome-dependent protein degradation after retrieval and is re-stabilized through a gene expression-dependent process known as memory reconsolidation. Memory reconsolidation after retrieval may be used to maintain or update long-term memories, reinforcing or integrating new information into them. However, the mechanisms underlying the reconsolidation of social and object recognition memory at the molecular and anatomical levels remain unknown. In this study, we try to understand the mechanisms for the update of social and object recognition memory through reconsolidation. To do this, we try to identify neural networks that regulate social and object recognition memory update. In addition, we examine the relationship between social and object recognition memory and neural activity by optogenetic techniques.

Selected Publication
  • Serita T, Fukushima H, Kida S: Constitutive activation of CREB in mice enhances temporal association learning and increases hippocampal CA1 neuronal spine density and complexity. Sci Rep, 7, 42528, 2017.
  • Yu Z, Fukushima H, Ono C, Sakai M, Kasahara Y, Kikuchi Y, Gunawansa N, Takahashi Y, Matsuoka H, Kida S, Tomita H: Microglial production of TNF-alpha is a key element of sustained fear memory. Brain Behav Immun, 59, 313-321, 2017.
  • Nonaka M, Kim R, Fukushima H, Sasaki K, Suzuki K, Okamura M, Ishii Y, Kawashima T, Kamijo S, Takemoto-Kimura S, Okuno H, Kida S, Bito H: Region-specific activation of CRTC1-CREB signaling mediates long-term fear memory. Neuron, 84, 92-106, 2014.
  • Fukushima H, Zhang Y, Archbold G, Ishikawa R, Nader K, Kida S: Enhancement of fear memory by retrieval through reconsolidation. Elife, 3, e02736, 2014.

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The neural mechanism for divergent sexuality

photo:Daisuke Yamamoto
Project leader

Advanced ICT Research Institute
National Institute of Information and Communications Technology
Principal Investigator Daisuke Yamamoto

Further information

Message from Project leader

We attempt at elucidating how genetic and environmental factors shape male sexual orientation in the fruit fly Drosophila, with special reference to the social-experience-dependent neural plasticity.

  • Project leader
    Principal InvestigatorDaisuke Yamamoto

    Advanced ICT Research Institute
    National Institute of Information and Communications Technology

    Research Area:
    Behavioral genetics, Neurogenetics

    E-mail:
    daichan*nict.go.jp
    (Please convert "*" into "@".)

Selected Publication
  • Yilmazer, Y. B., Koganezawa, M., Sato, K., Xu, J., Yamamoto, D. Serotonergic neuronal death and concomitant serotonin deficiency curb copulation ability of Drosophila platonic mutants. Nat. Commun. 7, 13792. doi: 10.1038/ncomms13792. 2016.
  • Kohatsu, S. and Yamamoto D. Visually induced initiation of Drosophila innate courtship-like following pursuit is mediated by central excitatory state. Nat. Commun. 6, 6457. doi:10.1038/ncomms7457. 2015.
  • Hamada-Kawaguchi, N., Nore, B. F., Kuwada, Y., Smith, C. I. and Yamamoto, D. Btk29A promotes Wnt4 signaling in the niche to terminate germ cell proliferation in Drosophila. Science 343, 294-297. 2014.
  • Yamamoto, D. and Koganezawa, M. Genes and circuits of courtship behavior in Drosophila males. Nat. Rev. Neurosci. 14, 681-692. 2013.
  • Sakurai, A., Koganezawa, M., Yasunaga, K., Emoto, K. and Yamamoto, D. Select interneuron clusters determine female sexual receptivity in Drosophila. Nat. Commun. 4, 1825-1833. 2013.
  • Ito H., Sato K., Koganezawa M., Ote M., Matsumoto K., Hama C. and Yamamoto D. Fruitless recruits two antagonistic chromatin factors to establish single-neuron sexual dimorphism Cell 149, 1327-1338. 2012.
  • Kohatsu, S., Koganezawa, M. and Yamamoto, D. Female contact activates male-specific interneurons that trigger stereotypic courtship behavior in a Drosophila male. Neuron 69, 498-508. 2011.
  • Kimura, K-I., Hachiya, T., Koganezawa, M., Tazawa, T. and Yamamoto, D. Fruitless and Doublesex coordinate to generate male-specific neurons that can initiate courtship. Neuron 59, 759-769. 2008.
  • Kimura, K-I., Ote, M., Tazawa, T. and Yamamoto, D. fruitless specifies sexually dimorphic neural circuitry in the Drosophila brain. Nature 438, 229-233. 2005.
  • Usui-Aoki, K., Ito, H., Ui-Tei, K., Takahashi, K. Lukacsovich, T., Awano, W., Nakata, H., Piao, Z. F., Nilsson, E., Tomida, J. and Yamamoto, D. Formation of the male-specific muscle in female Drosophila by ectopic fruitless expression. Nat. Cell Biol. 2, 500-506. 2000.

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Neural mechanism underlying generation of individual difference of learned vocalization by self-motivated practice

photo:Kazuhiro WADA
Project leader

Graduate School of Life Science, Hokkaido University
Associate Professor Kazuhiro WADA

Further information

Message from Project leader

Individual difference of learned behavior is regulated by both genetic information and developmental environment. Self-motivated practice is a critical driving factor for sensorimotor learning, such as human language acquisition and motor skill learning. The timing, quality, and amount of self-motivated practice crucially affect the final achievement and efficiency of learning. Birdsong, like human speech acquisition, is acquired through sensorimotor learning during a critical period in development. We have elucidated that epigenetic regulatory genes are induced by self-motivated vocal practice during song development. Based on this finding, we hypothesize the existence of epigenetic mechanisms for the transfer of the qualitative and quantitative values of self-motivated practice to vocal learning. In this research project, we will study the neural mechanism underlying the generation of individual differences in learned vocalization though the accumulation of self-motivated practice.

  • Project leader
    Associate ProfessorKazuhiro WADA

    Graduate School of Life Science, Hokkaido University

    Research Area:
    Behavioral neurobiology, Molecular neuroscience

    E-mail:
    wada*sci.hokudai.ac.jp
    (Please convert "*" into "@".)

    URL:
    https://www.wada-lab.org/

Selected Publication
  • Sato D, Mori C, Sawai A, Wada K: Familial bias and auditory feedback regulation of vocal babbling patterns during early song development. Scientific Reports, 6, 30323, 2016
  • Imai R, Sawai A, Hayase S, Furukawa H, Asogwa CN, Sanchez M, Wang H, Mori C, Wada K: A quantitative method for analyzing species-specific vocal sequence pattern and its developmental dynamics. Journal of Neuroscience Methods, 271, 25-33, 2016
  • Mori C, Wada K: Audition-Independent Vocal Crystallization Associated with Intrinsic Developmental Gene Expression Dynamics. Journal of Neuroscience, 35, 878-889, 2015
  • Ohgushi E, Mori C, Wada K: Diurnal oscillation of vocal development associated with clustered singing by juvenile songbirds. Journal of Experimental Biology. 218, 2260-2268, 2015
  • Liu WC, Wada K, Jarvis ED, Nottebohm F: Rudimentary substrates for vocal learning in a suboscine. Nature Communication, 4, 2082, 2013
  • Jarvis ED, Yu J, Rivas MV, Horita H, Feenders G, Whitney O, Jarvis S, Jarvis ER, Kubikova L, Puck AE, Siang-Bakshi C, Martin S, McElroy M, Hara E, Howard J, Mouritsen H, Chen CC, Wada K: A global view of the functional molecular organization of the avian cerebrum: Mirror images and functional columns. Journal of Comparative Neurology, 521, 3614-3665, 2013
  • Wada K, Hayase S, Imai R, Mori C, Kobayashi M, Liu WC, Takahasi M, Okanoya K: Differential androgen receptor expression and DNA methylation state in striatum song nucleus Area X between wild and domesticated songbird strains. European Journal of Neuroscience, 38, 2600-2610, 2013
  • Horita H, Kobayashi M, Liu WC, Oka K, Jarvis ED, Wada K: Specialized motor-driven dusp1 expression in the song systems of multiple lineages of vocal learning birds. PLoS ONE, 7, e42173, 2012
  • Wada K, Howard JT, McConnell P, Whitney O, Lints T, Rivas MV, Horita H, Patterson MA, White SA, Scharff C, Haesler S, Zhao S, Sakaguchi H, Hagiwara M, Shiraki T, Hirozane-Kishikawa T, Skene P, Hayashizaki Y, Carninci P, Jarvis ED: A molecular neuroethological approach for identifying and characterizing a cascade of behaviorally regulated genes. PNAS, 103, 15212-15217, 2006

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Neuronal mechanisms underlying individual differences in susceptibility and vulnerability to affective and aversive stimuli.

photo:Ayako M. Watabe
Project leader

Jikei University School of Medicine, Institute of Clinical Medicine and Research
Professor Ayako M. Watabe

Further information

Message from Project leader

Individual differences in susceptibility and vulnerability to affective and aversive stimuli are widely known, but their neuronal mechanisms are not well understood. For example, palatability of food are partly innately determined, while reward threshold of a certain stimuli to produce a hedonic response can be changed upon experiences. Likewise, even bitter taste, which typically induces aversive responses, can gradually grow to be rewarding by experiences as well, called acquired taste. Also, aversive stimuli can induce anxiety, leading to various kinds of defensive behaviors. The choice between passive defensive behaviors, such as freezing, and active defensive behaviors, such as fight or flight, is crucial for our survival strategies. While the choice between passive and active defensive responses is partly determined by the proximity of the threat, it is also modified by the previous behaviors as an adaptive responses and substantial individual differences are widely known. Such individual differences in rewarding and defensive systems compose part of the personalities and make our lives more colorful.
The aim of the present study is to elucidate the neuronal mechanisms underlying such individual differences in emotional responses. Especially, we focus on the amygdala neuronal circuits and their plasticity, which ultimately help better understanding of their physiological consequences.

  • Project leader
    ProfessorAyako M. Watabe

    Jikei University School of Medicine, Institute of Clinical Medicine and Research

    Research Area:
    Neuroscience, Electrophysiology, Behavioral Neuroscience

    E-mail:
    awatabe*jikei.ac.jp
    (Please convert "*" into "@".)

Selected Publication
  • Yokose, J., Okubo-Suzuki, R., Nomoto, M., Ohkawa, N., Nishizono, H., Suzuki, A., Matsuo, M., Tsujimura, S., Takahashi, Y., Nagase, M., Watabe, A.M., Sasahara, M., Kato, F., Inokuchi, K. Overlapping memory trace indispensable for linking, but not recalling, individual memories.
    Science, 355:398-403, 2017.
  • Sugimura, Y.K., Takahashi, Y., Watabe, A.M., Kato, F., Synaptic and network consequences of monosynaptic nociceptive inputs of parabrachial nucleus origin in the central amygdala.
    Journal of Neurophysiology 115: 2721-2739, 2016.
  • Watabe, A.M., Nagase, M., Hagiwara, A., Hida, Y., Tsuji, M., Ochiai, T., Kato, F., Ohtsuka, T. SAD-B Kinase regulates presynaptic vesicular dynamics at hippocampal Schaffer collateral synapses and affects contextual fear memory.
    Journal of Neurochemistry 136: 36-47, 2016.
  • Sato, M., Ito, M., Nagase, M., Sugimura, Y.K., Takahashi, Y., Watabe, A.M. #, Kato, F. The lateral parabrachial nucleus is actively involved in the acquisition of fear memory in mice.
    Molecular Brain 8:22, 1-15, 2015. (#CA) 
  • Watabe, A.M.#, Ochiai, T., Nagase, M., Takahashi, Y., Sato, M., Kato, F. Synaptic Potentiation in the Nociceptive Amygdala Following Fear Learning in Mice. 
    Molecular Brain 6: 11, 1-14, 2013. (#CA)
  • Kato, H.K., Watabe, A.M., Manabe, T. Non-Hebbian synaptic plasticity induced by repetitive postsynaptic action potentials.
    Journal of Neuroscience 29: 11153-11160, 2009.
  • Nakazawa, T.*, Komai, S.*, Watabe, A.M.*, Kiyama, Y., Fukaya, M., Arima-Yoshida, F., Horai, R., Sudo, K., Ebine, K., Delawary, M., Goto, J., Umemori, H., Tezuka, T., Iwakura, Y., Watanabe, M., Yamamoto, T. Manabe T. NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity. (*Equal contribution)
    EMBO Journal 25: 2867-2877, 2006.
  • Watabe, A.M., O’Dell, TJ. Age-related changes in theta frequency stimulation-induced long-term potentiation.
    Neurobiolgy of Aging 24: 267-272, 2003.
  • Watabe, A.M., Carlisle, H,J., O'Dell, T.J. Postsynaptic induction and presynaptic expression of group 1 mGluR-dependent LTD in the hippocampal CA1 region.
    Journal of Neurophysiology 87: 1395-1403, 2002.
  • Watabe, A.M., Zakki, P.A., O’Dell, T.J. Coactivation of beta-adrenergic and cholinergic receptors enhances the induction of long-term potentiation and synergistically activates mitogen-activated protein kinase in the hippocampal CA1 region.
    Journal of Neuroscience 20: 5924-5931, 2000.

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A03: Tools and theories for generative brain systems for individuality

Generation of humanized mouse models via genome editing to elucidate molecular basis for neurodevelopmental diversities

photo:Yukiko U. Inoue
Project leader

Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry
Researcher Yukiko U. Inoue

Further information

Message from Project leader

Autism spectrum disorders (ASDs) exhibit broad-ranging spectrum of symptoms as the name suggests. Similarly, there are no clear boundaries between moderate ASDs and individuals with typical development (TD). Even in sub-clinical populations, autistic-like traits (ALTs) are observed as ‘peculiarities’ in social communication skills, perception of self and others, and adaptations to the environment, that do not meet the formal criteria for ASDs. Here I focus on the ALT-associated gene loci that might explain neuronal basis for individualities or ‘kosei’, applying CRISPR/Cas9 genome editing technology and BAC transgenic technique to generate “humanized mouse models”. Sharing and analyzing the models in this field could elucidate the value of nucleotide changes in genome sequences to neurodevelopmental diversities. Also, I’d like to actively promote the collaborations with the members, providing the most advanced genome editing technology.

Humanized mouse models refer to those genome-edited mice obtained by knocking-out any mouse loci and knocking-in the corresponding human loci. In our whole genome, only a few percent of the sequences (genes) encode proteins, whereas the remaining regulatory sequences for gene expressions (enhancers) could contain a lot of information that leads to individual diversities. Since the nucleotide sequences of the regulatory regions are often not evolutionarily conserved between humans and mice, I aim a novel research approach by generating mouse models that retain human type gene regulations.

image
  • Project leader
    ResearcherYukiko U. Inoue

    Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry

    Research Area:
    Genome editing, Neurodevelopmental disorder

    E-mail:
    yinn3*ncnp.go.jp
    (Please convert "*" into "@".)

    URL:
    http://www.ncnp.go.jp/nin/guide/r6/index-lab2/

Selected Publication
  • Inoue YU and Inoue T: Brain enhancer activities at the gene-poor 5p14.1 autism-associated locus. Scientific Reports, 6, 31227, 2016
  • Ito Y, Inoue N, Inoue YU (equally contributed first author), Nakamura S, Matsuda Y, Inagaki M, Ohkubo T, Asami J, Terakawa YW, Kohsaka S, Goto Y, Akazawa C, Inoue T, Inoue K: Additive dominant effect of a SOX10 mutation underlies a complex phenotype of PCWH. Neurobiology of Disease, 80, 1-14, 2015 (Chosen as a cover article)
  • Hass MR, Liow HH, Chen X, Sharma A, Inoue YU Inoue T, Reeb A, Martens A, Fulbright M, Raju S, Stevens M, Boyle S, Park JS, Weirauch MT, Brent MR, Kopan R: SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers. Molecular Cell, 59(4), 685-697, 2015
  • Osterhout JA, Josten N, Yamada J, Pan F, Wu SW, Nguyen PL, Panagiotakos G, Inoue YU, Egusa SF, Volgyi B, Inoue T, Bloomfield SA, Barres BA, Berson DM, Feldheim DA, Huberman AD: Cadherin-6 mediated axon-target matching in a non-image-forming visual circuit. Neuron, 71, 632-639, 2011
  • Asami J, Inoue YU (equally contributed first author), Terakawa YW, Egusa SF, Inoue T: Bacterial artificial chromosomes as analytical basis for gene transcriptional machineries. Transgenic Research, 20, 913-924, 2011
  • Terakawa YW,Inoue YU Asami J, Inoue T: Bacterial artificial chromosome-based experimental strategies in the field of developmental Neuroscience. Bacterial Artificial Chromosome (InTech, ISBN 978-953-307-725-3), Chapter7, 103-118, 2011
  • Terakawa YW, Inoue YU Asami J, Hoshino M, Inoue T: A sharp cadherin-6 gene expression boundary in the developing mouse cortical plate demarcates the future functional areal border. Cerebral Cortex, 10, 2293-2308, 2013
  • Egusa SF, Inoue YU, Asami J, Terakawa YW, Hoshino M, Inoue T: Classic cadherin expressions balance postnatal neuronal positioning and dendrite dynamics to elaborate the specific cytoarchitecture of the mouse cortical area. Neuroscience Research, 105, 49-64, 2016

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Analysis of frequency and pattern of somatic mutation during early neural development

photo:Kazuya Iwamoto
Project leader

(Contributing as a collaborative member from 2018 July)

Department of Molecular Brain Science, Graduate School of Medical Sciences, Kumamoto University
Professor Kazuya Iwamoto

Further information

Message from Project leader

The cells in brain contain somatic mutations, which are generated through development by various mechanisms such as single nucleotide/ copy number variations, chromosomal aneuploidy, and retrotransposition. Somatic mutations in the brain cell modify the cellular functions, and may underlie the variation of human brain function and the pathophysiology of neuropsychiatric disorders. In this research project, our group explore frequency and pattern of somatic mutations occurring at early neural development by extensive exome analysis on the animal model.

  • Project leader (Contributing as a collaborative member from 2018 July)
    ProfessorKazuya Iwamoto

    Department of Molecular Brain Science, Graduate School of Medical Sciences, Kumamoto University

    Research Area:
    epigenetics, molecular psychiatry

    E-mail:
    iwamotok*kumamoto-u.ac.jp
    (Please convert "*" into "@".)

    URL:
    https://www.molbrain.com/

Selected Publication
  • Ueda J, Murata Y, Bundo M, Oh-Nishi A, Kassai H, Ikegame T, Zhao Z, Jinde S, Aiba A, Suhara T, Kasai K, Kato T, Iwamoto K: Use of human methylation arrays for epigenome research in the common marmoset (Callithrix jacchus). Neuroscience Research, in press
  • Bundo M, Toyoshima M, Okada Y, Akamatsu W, Ueda J, Nemoto-Miyauchi T, Sunaga F, Toritsuka M, Ikawa D, Kakita A, Kato M, Kasai K, Kishimoto T, Nawa H, Okano H, Yoshikawa T, Kato T, Iwamoto K: Increased L1 retrotransposition in the neuronal genome in schizophrenia. Neuron, 81, 306-313, 2014
  • Hayashi-Takagi A, Vawter MP, Iwamoto K: Peripheral biomarkers revisited: integrative profiling of peripheral samples for psychiatric research. Biological Psychiatry, 75, 920-928, 2014.
  • Nishioka M, Bundo M, Kasai K, Iwamoto K: DNA methylation in schizophrenia: progress and challenges of epigenetic studies. Genome Medicine, 4, 96, 2012.
  • Sugawara H, Iwamoto K, Bundo M, Ueda J, Miyauchi T, Komori A, Kazuno A, Adati N, Kusumi I, Okazaki Y, Ishigooka J, Kojima T, Kato T: Hypermethylation of serotonin transporter gene in bipolar disorder detected by epigenome analysis of discordant monozygotic twins. Translational Psychiatry, 1, e24, 2011.
  • Iwamoto K, Bundo M, Ueda J, Oldham MC, Ukai W, Hashimoto E, Saito T, Gescwind DH, Kato T: Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons. Genome Research, 21, 688-696, 2011.

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Analysis of formation processes of behavioral traits using dynamical hierarchical models

photo:Kentaro KATAHIRA
Project leader

Department of Psychology, Graduate School of Informatics, Nagoya University, Nagoya, Aichi, 464-8601, Japan.
Associate Professor Kentaro KATAHIRA

Further information

Message from Project leader

We aim to construct a novel analytical framework for investigating how individuality in behavioral traits are formed. We focus on the computational modeling approach, which uses mathematical models that represent latent computational processes underlying behaviors. The model parameter estimates can be used to characterize the behavioral traits of individuals. A hierarchical modeling approach, which incorporate the group-level distribution and individual level parameters, are useful for obtaining stable parameter estimates from group data of behaviors. In this project, we extend the hierarchical modeling approach, so that it can track the time course of the development of individual differences in behavioral traits. We apply the developed framework to behavioral data of rats to clarify how individual differences in anxiety-like behavior and flexibility to a changing environment are formed.

  • Project leader
    Associate ProfessorKentaro KATAHIRA

    Department of Psychology, Graduate School of Informatics, Nagoya University, Nagoya, Aichi, 464-8601, Japan.

    Research Area:
    Computational behavioral science, Psychology of learning

    E-mail:
    katahira*lit.nagoya-u.ac.jp
    (Please convert "*" into "@".)

    URL:
    http://profs.provost.nagoya-u.ac.jp/view/html/100007097_en.html

Selected Publication
  • Toyama A, Katahira K, & Ohira, H: A simple computational algorithm of model-based choice preference. Cognitive, Affective, & Behavioral Neuroscience, in press, 2017.
  • Katahira K: How hierarchical models improve point estimates of model parameters at the individual level. Journal of Mathematical Psychology, 73, 37-58, 2016.
  • Mizoguchi H, Katahira K, Inutsuka A, Fukumoto K, Nakamura A, Wang T, Nagai T, Sato J, Sawada M, Ohira H, Yamanaka A, Yamada K: Insular neural system controls decision-making in healthy and methamphetamine-treated rats. Proc. Natl. Acad. Sci. USA, 112 (29), E3930-E3939, 2015.
  • Katahira K: The relation between reinforcement learning parameters and the influence of reinforcement history on choice behavior. Journal of Mathematical Psychology, 66, 59–69, 2015.
  • Katahira K, Matsuda YT, Fujimura T, Ueno K, Asamizuya T, Suzuki C, Cheng K, Okanoya K, Okada M: Neural basis of decision-making guided by emotional outcomes. Journal of Neurophysiology, 113 (9), 3056-3068. 2015.
  • Bai Y, Katahira K, Ohira H: Valence-separated representation of reward prediction error in feedback-related negativity and positivity. Neuroreport, 26, 157–162. 2015.
  • Katahira K, Fujimura T, Matsuda YT, Okanoya K, Okada M: Individual differences in heart rate variability are associated with the avoidance of negative emotional events. Biological Psychology, 103, 322–331. 2014.
  • Katahira K, Suzuki K, Kagawa H, Okanoya K: A simple explanation for the evolution of complex song syntax in Bengalese finches. Biology Letters, 9, 20130842. 2013.
  • Katahira K, Okanoya K, Okada M: Statistical mechanics of reward-modulated learning in decision-making networks. Neural Computation, 24(5), 1230-1270. 2012.
  • Katahira K, Fujimura T, Okanoya K, Okada M: Decision-making based on emotional images. Frontiers in Psychology, 2, 311, 2011.

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Development of an optical method for defining an individuality of memory at the cellular level.

photo:Goto Akihiro
Project leader

Department of Pharmacology Kyoto University Graduate School of Medicine
Assistant professor Goto Akihiro

Further information

Message from Project leader

Although general mechanisms underlying memory have been revealed, cellular model which can account for individuality of memory hasn’t been demonstrated. Memory can be explained by the theory of cell assembly at the cellular level. In this theory, simultaneous activation of neuronal cells lead to an increase in synaptic strength among the cells. Based on this theory, I hypothesize that an individuality of memory is generated by the differences in the ability of forming cell assembly by inducing LTP. To test this hypothesis, I will develop a new optical technique which enable us to cancel LTP while observing neuronal activities by G-CaMP imaging at the same time in freely moving mice. By using this technique, spatio-temporal information of cell assembly in hippocampus CA1 and memory behavior will be acquired from the same mouse. The final goal of this project is to define an individuality of memory at the cellular level by examining correlation between cell assembly and memory behavior in the same mouse.

Selected Publication
  • Yamaguchi T, Goto A, Nakahara I, Yawata S, Hikida T, Matsuda M, Funabiki K, and Nakanishia S. Role of PKA signaling in D2 receptor-expressing neurons in the core of the nucleus accumbens in aversive learning. Proc Natl Acad Sci U S A. 112 (36):11383-11388. 2015.
  • Goto A, Nakahara I, Yamaguchi T, Kamioka Y, Sumiyama K, Matsuda M, Nakanishi S, and Funabiki K :Circuit-dependent striatal PKA and ERK signalings underlie behavioral shift in Male Mating Reaction. Proc Natl Acad Sci U S A. 112 (21):6718-23. 2015.
  • Goto A, Kamioka Y, Matsuda M : PKA modulation of Rac in neuronal cells.
    Front. Cell. Neurosci. 8:321. 2014
  • Ueyama, T., Sakaguchi, H., Nakamura, T., Goto A., Morioka, S. Shimizu, A., Nakao, K., Hishikawa, Y., Ninoyu, Y., Kassai, H., Suetsugu, J., Koji, T., Fritzsch, B., Yonemura, S., Hisa, Y., Matsuda, M., Aiba, A., and Saito, N : Maintenance of stereocilia and apical junctional complexes by Cdc42 in cochlear hair cells. J. Cell Sci. 127, 2040-2052. 2014
  • Nakamura T, Yasuda S, Nagai H, Koinuma S, Morishita S, Goto A, Kinashi T, and Wada N : Longest neurite-specific activation of Rap1B in hippocampal neurons contributes to polarity formation through RalA and Nore1A in addition to PI3-kinase. Genes Cells. 18(11):1020-31. 2013
  • Goto A, Kenta Sumiyama, Yuji Kamioka, Eiji Nakasyo, Keisuke Ito, Mitsuhiro Iwasaki, Hideki Enomoto, Michiyuki Matsuda : GDNF and Endothelin 3 regulate migration of enteric neural crest-derived cells via protein kinase A and Rac1. J Neurosci. 33(11):4901-4912. 2013
  • Goto A, Hoshino M, Matsuda M, Nakamura T : Phosphorylation of STEF/Tiam2 by protein kinase A is critical for Rac1 activation and neurite outgrowth in dibutyryl cAMP-treated PC12D cells. Mol Biol Cell. 22:1780-90. 2011.

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Synaptic mechanisms underlying individual differences in anxiety

photo:Katsunori Kobayashi
Project leader

Department of Pharmacology, Nippon Medical School
Associate Professor Katsunori Kobayashi

Further information

Message from Project leader

The goal of my research is to reveal the cellular and synaptic basis underlying individual differences in mouse behavior and to translate it to treatments for psychiatric disorders. So far I have analyzed the neuronal phenotypes of many lines of mouse models of psychiatric disorders. During the course of these studies, I have found that a particular function of the hippocampal synapses correlates with a form of anxiety-related behavior in individual mice, which suggests a possibility that individual differences in anxiety of mice is determined by the particular synapse. At present, however, it is unknown whether such correlation represents a causal relationship between behavior and synaptic transmission. It is also unknown whether such relationship is observed only in some disease models or generally observed, possibly in healthy mice as well. In the present study, I will examine whether individual differences in anxiety-like behavior of mice can be actually explained by individual differences in hippocampal synaptic functions.

  • Project leader
    Associate ProfessorKatsunori Kobayashi

    Department of Pharmacology, Nippon Medical School

    Research Area:
    Neurophysiology, Neuroscience

    E-mail:
    kkatsu-tky*umin.ac.jp
    (Please convert "*" into "@".)

    URL:
    http://www2.nms.ac.jp/nms/pharmacol/

Selected Publication
  • Kobayashi K, Imoto Y, Yamamoto F, Kawasaki M, Ueno M, Segi-Nishida E, Suzuki H: Rapid and lasting enhancement of dopaminergic modulation at the hippocampal mossy fiber synapse by electroconvulsive treatment. Journal of Neurophysiology, 117, 284-289, 2017
  • Kobayashi K, Ikeda Y, Asada M, Inagaki H, Kawada T, Suzuki H: Corticosterone facilitates fluoxetine-induced neuronal plasticity in the hippocampus. PLoS One, 8, e63662, 2013
  • Kobayashi K, Haneda E, Higuchi M, Suhara T, Suzuki H: Chronic fluoxetine selectively upregulates dopamine D1-like receptors in the hippocampus. Neuropsychopharmacology, 37, 1500-1508, 2012
  • Kobayashi K, Umeda-Yano S, Yamamori H, Takeda M, Suzuki H, Hashimoto R: Correlated alterations in serotonergic and dopaminergic modulations at the hippocampal mossy fiber synapse in mice lacking dysbindin. PLoS One, 6, e18113, 2011
  • Kobayashi K, Ikeda Y, Suzuki H: Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine. Molecular Brain, 4, 12, 2011
  • Kobayashi K, Ikeda Y, Sakai A, Yamasaki N, Haneda E, Miyakawa T, Suzuki H: Reversal of hippocampal neuronal maturation by serotonergic antidepressants. Proceedings of the National Academy of Sciences USA, 107, 8434-8439, 2010
  • Kobayashi K, Ikeda Y, Haneda H, Suzuki H: Chronic fluoxetine bidirectionally modulates potentiating effects of serotonin on the hippocampal mossy fiber synaptic transmission. Journal of Neuroscience, 28, 6272-6280, 2008
  • Kobayashi K, Ikeda Y, Suzuki H: Locomotor activity correlates with modifications of hippocampal mossy fibre synaptic transmission. European Journal of Neuroscience, 24, 1867-1873, 2006
  • Kobayashi K, Poo M-m: Spike train timing-dependent associative modification of hippocampal CA3 recurrent synapses by mossy fibers. Neuron, 41, 445-454, 2004
  • Kobayashi K, Manabe T, Takahashi T: Presynaptic long-term depression at the hippocampal mossy fiber-CA3 synapse. Science, 273, 648-650, 1996

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Development and application of dendritic spine imaging for elucidating mechanism of individuality formation.

photo:Masayuki Sakamoto
Project leader

Graduate School of Medicine, The University of Tokyo
Assistant Professor Masayuki Sakamoto

Further information

Message from Project leader

Genetic and environmental factors are considered to be involved in individuality formation. Among these factors, child rearing during the postnatal developmental period is one of the most important factors affecting children’s individuality formation. However, the impact of child rearing and how this affects children’s immature neural circuits and their individuality formation is not well understood. One of the reasons is that a method to observe the process of individuality emergence has not been established. Here, as a new technique to elucidate the mechanism of individuality formation, we develop an imaging method to observe morphology and activity of neurons during postnatal developmental period. By utilizing genetically encoded calcium/voltage indicators with two-photon microscopy, we aim to understand neural activity at single spine resolution. I hope this imaging technique will not only clarify the impact of rearing on children’s individuality formation, but also obtain fundamental knowledge to build ideal relationships between parents and their children.

  • Project leader
    Assistant ProfessorMasayuki Sakamoto

    Graduate School of Medicine, The University of Tokyo

    Research Area:
    Imaging, Neuroscience

    E-mail:
    msakamoto*m.u-tokyo.ac.jp
    (Please convert "*" into "@".)

    URL:
    http://www.neurochem.m.u-tokyo.ac.jp/Homepage.html

Selected Publication
  • Sakamoto M, Ieki N, Miyoshi G, Mochimaru D, Miyachi H, Imura T, Yamaguchi M, Fishell G, Mori K, Kageyama R, Imayoshi I: Continuous postnatal neurogenesis contributes to the formation and maintenance of the functional olfactory bulb neural circuits. Journal of Neuroscience, 34: 5788-5799, 2014.
  • Sakamoto M, Kageyama R, Imayoshi I: The functional significance of newly born neurons integrated into olfactory bulb circuits. Frontiers in Neuroscience, 8, 121, 2014.
  • Sakamoto M, Imayoshi I, Ohtsuka T, Yamaguchi M, Mori K, Kageyama R: Continuous neurogenesis in the adult forebrain is required for innate olfactory responses. Proceedings of the National Academy of Sciences, 108: 8479-8484, 2011.
  • Imayoshi I, Sakamoto M, Yamaguchi M, Mori K, Kageyama R. Essential roles of Notch signaling in maintenance of neural stem cells in developing and adult brains. Journal of Neuroscience 30: 3489-3498, 2010.
  • Imayoshi I, Sakamoto M, Ohtsuka T, Miyakawa T, Takao K, Mori K, Yamaguchi M, Ikeda T, Itohara T, Kageyama R, Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nature Neuroscience 11: 1153-1161, 2008.

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Large-scale analysis of central-peripheral interactions underlying individual differences

photo:Takuya Sasaki
Project leader

Graduate School of Pharmaceutical Sciences, The University of Tokyo
Assistant Professor Takuya Sasaki

Further information

Message from Project leader

This study examines how individual differences of mental stress responses are expressed through the interaction between the brain and peripheral organs. To address this issue, we first develop a novel method to record extracellular field potential signals from a wide range of brain regions, including the neocortex, hippocampus, and amygdala, together with body rhythmic signals such as electrocardiograms, electromyograms, and breathing signals from a freely moving rodent. This method is applied to animals that are subject to a social defeat, a experimental model inducing large individual differences of stressful responses. In the large-scale data of systemic signals, we especially focus on power changes in the local field potentials and multiunit spiking patterns of neuronal ensembles by comparing a variety of physiological body states represented by cardiac and breathing systems. The evidence advances our understanding of the neurophysiological mechanisms how individual differences in response to mental stress exposure is expressed at the level of mind-body associations.

image
  • Project leader
    Assistant ProfessorTakuya Sasaki

    Graduate School of Pharmaceutical Sciences, The University of Tokyo

    Research Area:
    Neurophysiology, Neuropharmacology

    E-mail:
    tsasaki*mol.f.u-tokyo.ac.jp
    (Please convert "*" into "@".)

    URL:
    http://sasaki-brain.net/

Selected Publication
  • Sasaki T*, Nishimura Y, Ikegaya Y: Simultaneous recordings of central and peripheral bioelectrical signals in a freely moving rodent. Biological and Pharmaceutical Bulletin, in press.
  • Igata H, Sasaki T*, Ikegaya Y*: Ealry failures benefit subsequent task performance. Scientific Reports, 6, 21293, 2016.
  • Sasaki T, Leutgeb S, Leutgeb JK*: Spatial and memory circuits in the medial entorhinal cortex. Current Opinion in Neurobiology, 32, 16-23, 2015.
  • Beppu K+, Sasaki T+, Tanaka KF, Yamanaka A, Fukazawa Y, Shigemoto R, Matsui K*: Optogenetic countering of glial acidosis supresses glial glutamate release and ischemic brain damage. Neuron, 81, 314-320, 2014.
  • Sasaki T*: The axon as a unique computational unit in neurons. Neuroscience Research, 75, 83-88, 2013.
  • Sasaki T+, Beppu K+, Tanaka KF, Fukazawa Y, Shigemoto R, Matsui K*: Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation. Proceedings of the National Academy of Sciences of the United States of America, 109, 20720-20725, 2012.
  • Sasaki T*, Matsuki N, Ikegaya Y: Targeted axon-attached recording with fluorescent patch-clamp pipettes in brain slices. Nature Protocols, 7, 1228-1234, 2012.
  • Sasaki T, Matsuki N, Ikegaya Y*: Effects of axonal topology on the somatic modulation of synaptic outputs. Journal of Neuroscience, 32, 2868-2876, 2012.
  • Sasaki T, Matsuki N, Ikegaya Y*: Action potential modulation during axonal conduction. Science, 331, 599-601, 2011.
  • Sasaki T, Kuga N, Namiki S, Matsuki N, Ikegaya Y*: Locally synchronized astrocytes. Cerebral Cortex, 21: 1889-1900, 2011.

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