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Researcher Information

last modified:2017/05/23

Associate Professor HASHIMOTO Takanori

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Faculty, Affiliation

Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences
Associate Professor

College and School Educational Field

Division of Medical Sciences, Graduate School of Medical Science
Division of Neuroscience, Graduate School of Medical Science
School of Medicine, College of Medical, Pharmaceutical and Health Sciences

Laboratory

Department of Psychiatry and Neurobiology TEL:076-265-2301 FAX:076-234-4254

Academic Background

【Academic background(Doctoral/Master's Degree)】
Graduate School for Advanced Studies Doctor Department of Physiological Sciences 199203 Completed
【Academic background(Bachelor's Degree)】
Niigata University School of Medicine 198903
【Degree】
M.D.
Ph.D.

Career

Research Associate, Laboratory of Neurochemistry, National Institute for Physiological sciences, Okazaki/Japan National Institute for Physiological Sciences(1992/04/01-1993/03/31)
Research Scientist, Mind Articulation Project, Japan Science and Technology Corporation, Tokyo/Japan(1997/04/01-2000/08/31)
Postdoctoral Fellow, Department of Psychiatry, University of Pittsburgh(2000/09/07-2003/06/30)
Assistant Professor, Department of Psychiatry, University of Pittsburgh(2003/07/01-2007/04/30)

Year & Month of Birth

Academic Society

The Japanese Society of Psychiatry and Neurology
Society for Neuroscience
Society of Biological Psychiatry
Japan Neuroscience Society

Award

○Best Research Award(2009/02/07)
○Young Investigator Award(2006/07/01)
○The Sidney R Baer JR Prize(2005/10/30)
○Young Investigator Award(2004/07/01)
○Travel Award for Excellent Presentation(2005/08/05)
○Best Poster Award(2003/02/01)
○Best Oral Presentation Award at WPIC Research Day(2003/06/07)

Specialities

Pathophysiology of Cognitive Deficits in Schizophrenia

Speciality Keywords

Schizophrenia, Cerebral Cortex, Pathophysiology

Research Themes

Neural Basis of Cognitive Dysfunction in Schizophrenia

Neural Basis of Cognitive Dysfunction in Schizophrenia Schizophrenia is a severe mental disorder that affects about 1% of the world’s population. The pathogenesis of this illness is thought to start during early brain development and affected individuals often come to clinical attention during late adolescence and early adulthood. Psychotic symptoms, such as delusion, hallucination, and disorganized behavior, are a striking feature of this disorder. However, even more serious problem for patients is chronic impairments in social and occupational functioning, and these impairments are associated with cognitive deficits. Patients typically exhibit deficits in diverse cognitive functions, such as sensory processing, working memory, and executive function. They are resistant to currently available treatments and they are a key determinant of patients’ functional outcome.

Human cognitive functions are mediated by neural networks that consist of multiple brain regions, including different areas of the cerebral cortex. These areas are connected by axons of projecting neurons, and information processing within each and across these areas is facilitated by neural oscillations, which reflect coordinated activities of local neuron assemblies. Neural oscillations were shown to promote local information processing and global information processing through their inter-areal synchronization. Neural oscillations depend on one of the three subsets of cortical GABA neurons, that is the parvalbumin (PV)-expressing subset. PV neurons furnish divergent inhibitory innervations to neighboring pyramidal neurons and can synchronize firing of these neurons (Figure 1).

KCNS3 encodes a voltage-gated potassium channel subunit and is selectively expressed in PV neurons in the human cerebral cortex. KCNS3 subunit-containing potassium channels make EPSP fast in PV neurons and appear to contribute to neural oscillations (Figure 2). We have recently found that KCNS3 and KCNB1 expression levels were lower in prefrontal PV neurons in schizophrenia. Reduced KCNS3 subunit-containing channels could make EPSP slow in PV neurons and contribute to abnormal neural oscillations and cognitive deficits in schizophrenia.

In order to prove our hypothesis of KCNS3 in the pathophysiology of schizophrenia and to identify molecular targets of new therapeutic intervention for cognitive impairments, we are currently generating genetically engineered mice with PV neuron selective knockout of Kcns3. We will analyze neural oscillations and cognitive functions in these mice.

Books

  •  Lewis DA, Hashimoto T, Maldonado-Aviles JG, Morris H Cortical Deficits in Schizophrenia: From Genes to Function  Springer 2008
  •  Hashimoto T and Lewis DA The Postmortem Brain in Psychiatric Research  Kluwer Academic Publishers 2002

Papers

  •  Cortical gene expression after a conditional knockout of 67 kDa glutamic acid decarboxylase in parvalbumin neurons Georgiev D, Yoshihara T, Kawabata R, Matsubara T, Tsubomoto M, Minabe Y, Lewis DA, Hashimoto T Schizophrenia Bulletin 42 992-1002 2016
  •  Reduced prefrontal activation during performance of the Iowa Gambling Task in patients with bipolar disorder Ono Y, Kikuchi M, Hirosawa T, Hino S, Nagasawa T, Hashimoto T, Munesue T, Minabe Y Psychiatry Research 233 1-8 2015
  •  Reduced long-range functional connectivity in young children with autism spectrum disorder Kikuchi M, Yoshimura Y, Hiraishi H, Munesue T, Hashimoto T, Tsubokawa T, Takahashi T, Suzuki M, Higashida H, Minabe Y Socal Cognitive and Affective Neuroscience  10 248-254 2015
  •  Lower gene expression for KCNS3 potassium channel subunit in parvalbumin-containing neurons in the prefrontal cortex of subjects with schizophrenia  Georgiev D, Arion D, Enwright JF, Kikuchi M, Minabe Y, Corradi JP, Lewis DA, Hashimoto T American Journal of Psychiatry 171 62-71 2014
  •  Deficit in transcriptional regulators in cortical parvalbumin neurons in schizophrenia  Volk DW*, Matsubara T*, Li S, Sengupta EJ, Georgiev D, Minabe Y, Sampson A, Hashimoto T, Lewis DA.  American Journal of Psychiatry 169 1082 2012

show all

  •  Selective Expression of KCNS3 Potassium Channel α-Subunit in Parvalbumin-Containing GABA Neurons in the Human Prefrontal Cortex Georgiev D, González-Burgos G, Kikuchi M, Minabe Y, Lewis DA and Hashimoto T. PLoS ONE 7 e43904 2012
  •  Oxytocin attenuates feelings of hostility depending on emotional context and individuals’ characteristics Hirosawa T, Kikuchi M, Higashida H, Okumura E, Ueno S, Shitamichi K, Yoshimura Y, Munesue T, Tsubokawa T, Haruta Y, Nakatani H, Hashimoto T, Minabe Y.  Scientific Reports 2 384 2012
  •  Frontal areas contribute to reduced global coordination of resting-state gamma activities in drug-naive patients with schizophrenia Kikuchi M, Hashimoto T, Nagasawa T, Hirosawa T, Minabe Y, Yoshimura M, Strik W, Dierks T, Koenig T Schizophrenia Research 130 187 2011
  •  Lamina-specific Alterations in Cortical GABAA Receptor Subunit Expression in Schizophrenia Beneyto M, Abbott A ,Hashimoto T, Lewis DA Cerebral Cortex 21 999-1101 2011
  •  Neurovascular coupling in the human somatosensory cortex: a single trial study Kikuchi M, Shitamichi K ,Ueno S, Yoshimura, Remijn GB, Nagao K, Munesue T, Iiyama K, Tsubokawa T, Haruta Y, Inoue Y, Watanabe K, Hashimoto T, Higashida H, Minabe Y.  Neuroreport 21 1106 2010
  •  Protracted Postnatal Developmental Trajectories of GABAA Receptor α1 and α2 subunit Expression in Primate Prefrontal Cortex Hashimoto T, Nugyen QL, Rotaru D, Keenan T, Arion D, Beneyto M, Gonzalez-Burgos G, Lewis DA Biological Psychiatry 65 1015 2009
  •  Altered Markers of Tonic Inhibition in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia. Maldonado-Avilés JG, Curley AA, Hashimoto T, Lewis DA American Journal of Psychiatry 166 450 2009
  •  A neonatal ventral hippocampal lesion causes functional deficits in adult prefrontal cortical neurons Tseng K, Lewis B, Hashimoto T,Sesack S, Kloc M, Lewis DA, and O'Donnell P Journal of Neuroscience 28 12691 2008
  •  Reduced cortical cannabinoid 1 receptor mRNA and protein expression in schizophrenia Eggan SM, Hashimoto T, Lewis DA Arch Gen Psychiatry  165 772-784 2008
  •  Conserved Regional Patterns of GABA-Related Transcript Expression in the Neocortex of Subjects with Schizophrenia Hashimoto T, Bazmi HH ,Mirnics K, Wu Q, Sampson AR, and Lewis DA American Journal of Psychiatry 165 479-489 2008
  •  Alterations in somatostatin mRNA expression in the dorsolateral prefrontal cortex of subjects with schizophrenia Morris HM, Hashimoto T, Lewis DA Cerebral Cortex 18 1575-1587 2008
  •  Alterations in GABA-Related Transcriptome in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia Hashimoto T, Arion D, Unger T, Maldonado-Avilés JG, Morris HM, Volk DW, Mirnics K, and Lewis DA Molecular Psychiatry 13 147-161 2008
  •  Cell and Receptor Type-Specific Alterations in Markers of GABA Neurotransmission in the Prefrontal Cortex of Subjects with Schizophrenia. Lewis DA, Hashimoto T, Morris HM. Neurotoxicology  14 237-248 2008
  •  Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood Glorioso C, Sabatini M, Unger T, Hashimoto T, Monteggia LM, Lewis DA, Mirnics K Molecular Psychiatry 11 633-648 2006
  •  Molecular Mechanisms Contributing to Dendritic Spine Alterations in the Prefrontal Cortex of Subjects with Schizophrenia Hill JJ, Hashimoto T and Lewis DA Molecular Psychiatry 11 557-566 2006
  •  BDNF Val66Met polymorphism and GAD67 mRNA expression in the prefrontal cortex of subjects with schizophrenia Hashimoto T and Lewis DA American Journal of Psychiatry  163 534-537 2006
  •  Cortical Inhibitory Neurons and Schizophrenia Lewis DA, Hashimoto T, Volk DW Nature Review Neuroscience  6 312-324 2005
  •  Analysis of Pyramidal Neuron Morphology in an Inducible Knockout of Brain Derived Neurotrophic Factor Hill J, Kolluri N, Hashimoto T, Wu Q, Sampson AR, Monteggia LM, and Lewis DA Biological Psychiatry 57 932-934 2005
  •  Relation of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia Hashimoto T, Bergen SE, Nguyen QL, Xu B, Monteggia LM, Pierri JN, Sun Z, Sampson AR, and Lewis DA Journal of Neuroscience  25 372-383 2005
  •  Selective alterations in prefrontal cortical GABA neurotransmission in schizophrenia: a novel target for the treatment of working memory dysfunction. Lewis DA, Volk DW, Hashimoto T Psychopharmacology (Berl) 174 143-150 2004
  •  Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia Hashimoto T, Volk DW, Eggan, SM, Mirnics K, Pierri, JN, Sun Z, Sampson AR, and Lewis DA Journal of Neuroscience  26 6315-6326 2003
  •  Selective zif268 mRNA induction in the perirhinal cortex of macaque monkeys during formation of visual pair-association memory Tokuyama W, Okuno H, Hashimoto T, Li YX, and Miyashita Y Journal of Neurochemistry  81 60-70 2002
  •  Differential induction of brain-derived neurotrophic factor mRNA in rat inferior olive subregions following unilateral labyrinthectomy Li YX, Tokuyama W, Okuno H, Miyashita Y and Hashimoto T Neuroscience  106 385-394 2001
  •  BDNF upregulation during declarative memory formation in the monkey inferior temporal cortex Tokuyama W, Okuno H, Hashimoto T, Li YX and Miyashita Y Nature Neuroscience 3 1134-1142 2000
  •  Spatio-temporal dynamics of BDNF mRNA induction in the vestibulo-olivary network during vestibular compensation Li YX, Hashimoto T, Tokuyama W, Miyashita Y and Okuno H Journal of Neuroscience 21 2738-2748 2001
  •  Expression of brain-derived neurotrophic factor and their receptor messenger RNAs in monkey rhinal cortrex Hashimoto T, Okuno H, Tokuyama W, Li YX, Miyashita Y Neuroscience 95 1003-1010 2000
  •  Quantification of neurotrophin-3 mRNA in the rat hippocampal subregions using the RT-PCR-based coamplification method Tokuyama W, Hashimoto T, Li YX, Okuno H, Miyashita Y Brain Research Protocols 4 407-414 1999
  •  Quantitative evaluation of neurotrophin and trk mRNA expression in visual and limbic areas along the occipito-temporo-hippocampal pathway in adult macaque monkeys Okuno H, Tokuyama W, Li YX, Hashimoto T, Miyashita Y Journal of Comparative Neurology 408 378-398 1999
  •  Highest trkB mRNA expression in the entorhinal cortex among hippocampal subregions in the adult rat: contrasting pattern with BDNF mRNA expression Tokuyama W, Hashimoto T, Li YX, Okuno H, Miyashita Y Molecular Brain Research 62 206-215 1998
  •  Psychotomimetic-induction of tissue plasminogen activator mRNA in corticostriatal neurons in rat brain Hashimoto T, Kajii Y, Nishikawa T European Journal of Neuroscience 10 3387-3399 1998
  •  Methamphetamine-induced dopaminergic hyperactivity is not accompanied with increase in tyrosine hydroxylase mRNA of the rat midbrain Ishimaru M, Hashimoto T, Obata K, Fukamauchi F Neuroscience Letter  191 107-110 1995
  •  Increase of tyrosine hydroxylase and its mRNA in the rat substantia nigra pars reticulata by diazepam and picrotoxin Stork O, Hashimoto T, Obata K Neuroscience Research  19 73-80 1994
  •  Haloperidol activates tyrosine hydroxylase gene-expression in the rat substantia nigra, pars reticulata Stork O, Hashimoto T, Obata K Brain Research 633 213-222 1994
  •  Stimulus-transcription coupling can be studied in situ hybridization of brain slice preparation: selective c-fos expression in Hippocampal CA3 pyramidal cells Sekino,Y, Hashimot T, Obata K Proceedings of the Japan Academy Series B-Physical and Biological Sciences 63 191-195 1992
  •  Induction of somatostatin by kainic acid in pyramidal and granule cells of the rat hippocampus Hashimoto T, Obata K Neuroscience Research 12 514-527 1991
  •  Alteration of Cortical GABA Neurons and Network Oscillations in Schizophrenia Current Psychiatry Report 12 335 2010
  •  Deciphering the Disease Process of Schizophrenia: The Contribution of Cortical GABA Neurons. Lewis DA, Hashimoto T Intertnational Review of Neurobiology 78 109-131 2007
  •  Inhibition and Timing in Cortical Neural Circuits Gonzalez-Burgos, G, Hashimoto T, Lewis DA American Journal of Psychiatry  164 12 2007
  •  GABA neurons in the human prefrontal cortex Hashimoto T, Volk DW, Lewis DA American Journal of Psychiatry  161 1764 2004
  •  Neurochemical analysis of the tyrosine hydroxylase expression in methamphetamine-sensitized rats Fukamauchi F, Ishimaru M, Hashimoto T, Obata K. Annals of the New York Academy of Sciences 801 371-376 1996

Conference Presentations

Arts and Fieldwork

Patent

Theme to the desired joint research

Grant-in-Aid for Scientific Research

○Grant-in-Aid for Scientific Research (B)「Cognitive Deficits and Oxytocin Signaling in Parvalbumin Neurons in Schizophrenia」(2016-2018) 
○Grant-in-Aid for Scientific Research on Innovative Areas「Neural Network Dysfunction in Schizophrenia and KCNS3 Deficits in Parvalbumin Neurons」(2015-2016) 
○Grant-in-Aid for Challenging Exploratory Research「GABRA1 GABA Receptor Gene and Alterations in Cortical Inhibitory Neurons in Schizophrenia」(2014-2015) 
○Grant-in-Aid for Scientific Research (B)「Kv9.3 Potassium Channel Subunit and Cortical Dysfunction in Schizophrenia」(2013-2015) 
○Grant-in-Aid for Scientific Research on Innovative Areas「Survey of Altered Kv9.3 Potassium Channel Subunit Expression across Brain Regions in Subjects with Schizophrenia」(2013-2014) 
○Grant-in-Aid for Challenging Exploratory Research「 Analysis of Basal Ganglia Neurons in Schizophrenia」(2012-2013) 
○Grant-in-Aid for Challenging Exploratory Research「Cortical Functional Connectivity in Schizophrenia」(2010-2011) 
○Grant-in-Aid for Scientific Research (B)「Molecular mechanism of altered cannabinoid signaling in the pathophysiology of schizophrenia」(2009-2011) 
○Grant-in-Aid for Host Researcher of Foreign Postdoctoral Fellow「Identification of affected cortical GABA neuron subsets in schizophrenia」(2009-2010) 

Classes (Bachelors)

Classes (Graduate Schools)

○General Psychiatry(2017)
○Dementia Conference 2(2017)
○Special Lectures of Dementia(2017)
○Dementia Conference 2(2017)
○Dementia Conference 3(2017)
○Dementia Conference 3(2017)
○Treatment and Prevention of Dementia(2017)
○General Psychiatry(2017)
○Dementia Conference 4(2017)
○Dementia Conference 1(2017)
○Dementia Conference 4(2017)
○Dementia Conference 1(2017)
○Treatment and Prevention of Dementia(2017)
○Neuroscience Seminar(2016)
○Dementia Conference 1(2016)
○Dementia Conference 2(2016)
○Dementia Conference 4(2016)
○General Psychiatry(2016)
○Dementia Conference 1(2016)
○Special Lectures of Dementia(2016)
○Dementia Conference 3(2016)
○Treatment and Prevention of Dementia(2016)
○Treatment and Prevention of Dementia(2016)
○Dementia Conference 2(2016)
○Dementia Conference 3(2016)
○General Psychiatry(2016)
○Dementia Conference 4(2016)

International Project

International Students

Lecture themes

Others (Social Activities)

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