PhysiologyⅡ

Mahito Ohkuma

  (大熊 真人)

Profile Information

Affiliation
School of Medicine Faculty of Medicine, Fujita Health University
Degree
Ph.D(*Himeji Institute of Technology*)

J-GLOBAL ID
200901080823507854
researchmap Member ID
1000306282

External link

Research Interests

 2

Papers

 33
  • Masahiro Kawatani, Kayo Horio, Mahito Ohkuma, Wan-Ru Li, Takayuki Yamashita
    The Journal of Neuroscience, JN-RM, Dec 1, 2023  
    Body movements influence brain-wide neuronal activities. In the sensory cortex, thalamocortical bottom-up inputs and motor-sensory top-down inputs are thought to affect the dynamics of membrane potentials (Vm) of neurons and change their processing of sensory information during movements. However, direct perturbation of the axons projecting to the sensory cortex from other remote areas during movements has remained unassessed, and therefore the interareal circuits generating motor-related signals in sensory cortices remain unclear. Using a Gi-coupled opsin, eOPN3, we here inhibited interareal signals incoming to the whisker primary somatosensory barrel cortex (wS1) of awake male mice and tested their effects on whisking-related changes in neuronal activities in wS1. Spontaneous whisking in air induced the changes in spike rates of a fraction of wS1 neurons, which were accompanied by depolarization and substantial reduction of slow-wave oscillatory fluctuations of Vm. Despite an extensive innervation, inhibition of inputs from the whisker primary motor cortex (wM1) to wS1 did not alter the spike rates and Vmdynamics of wS1 neurons during whisking. In contrast, inhibition of axons from the whisker-related thalamus (wTLM) and the whisker secondary somatosensory cortex (wS2) to wS1 largely attenuated the whisking-related supra- and sub-threshold Vmdynamics of wS1 neurons. Notably, silencing inputs from wTLM markedly decreased the modulation depth of whisking phase-tuned neurons, while inhibiting wS2 inputs did not impact the whisking variable tuning of wS1 neurons. Thus, sensorimotor integration in wS1 during spontaneous whisking is predominantly facilitated by direct synaptic inputs from wTLM and wS2 rather than from wM1. Significance statementThe traditional viewpoint underscores the importance of motor-sensory projections in shaping movement-induced neuronal activity within sensory cortices. However, this study challenges such established views. We reveal that the synaptic inputs from the whisker primary motor cortex do not alter the activity patterns and membrane potential dynamics of neurons in the whisker primary somatosensory cortex (wS1) during spontaneous whisker movements. Furthermore, we make a novel observation that inhibiting inputs from the whisker secondary somatosensory cortex (wS2) substantially curtails movement-related activities in wS1, leaving the tuning to whisking variables unaffected. These findings provoke a reconsideration of the role of motor-sensory projections in sensorimotor integration and bring to light a new function for wS2-to-wS1 projections.
  • Noriko Hiramatsu, Naoki Yamamoto, Mahito Ohkuma, Noriaki Nagai, Ei-Ichi Miyachi, Kumiko Yamatsuta, Kazuyoshi Imaizumi
    Medical molecular morphology, 55(4) 292-303, Aug 6, 2022  
    When regenerated tissue is generated from induced pluripotent stem cells (iPSCs), it is necessary to track and identify the transplanted cells. Fluorescently-labeled iPSCs synthesize a fluorescent substance that is easily tracked. However, the expressed protein should not affect the original genome sequence or pluripotency. To solve this problem, we created a cell tool for basic research on iPSCs. Iris tissue-derived cells from GFP fluorescence-expressing mice (GFP-DBA/2 mice) were reprogrammed to generate GFP mouse iris-derived iPSCs (M-iris GFP iPSCs). M-iris GFP iPSCs expressed cell markers characteristic of iPSCs and showed pluripotency in differentiating into the three germ layers. In addition, when expressing GFP, the cells differentiated into functional recoverin- and calbindin-positive cells. Thus, this cell line will facilitate future studies on iPSCs.
  • Miho Kawata, Yu Kodani, Mahito Ohkuma, Ei-Ichi Miyachi, Yoko S Kaneko, Akira Nakashima, Hidetaka Suga, Toshiki Kameyama, Kanako Saito, Hiroshi Nagasaki
    PloS one, 17(11) e0276694, 2022  
    The hypothalamus is comprised of heterogenous cell populations and includes highly complex neural circuits that regulate the autonomic nerve system. Its dysfunction therefore results in severe endocrine disorders. Although recent experiments have been conducted for in vitro organogenesis of hypothalamic neurons from embryonic stem (ES) or induced pluripotent stem (iPS) cells, whether these stem cell-derived hypothalamic neurons can be useful for regenerative medicine remains unclear. We therefore performed orthotopic transplantation of mouse ES cell (mESC)-derived hypothalamic neurons into adult mouse brains. We generated electrophysiologically functional hypothalamic neurons from mESCs and transplanted them into the supraoptic nucleus of mice. Grafts extended their axons along hypothalamic nerve bundles in host brain, and some of them even projected into the posterior pituitary (PPit), which consists of distal axons of the magnocellular neurons located in hypothalamic supraoptic and paraventricular nuclei. The axonal projections to the PPit were not observed when the mESC-derived hypothalamic neurons were ectopically transplanted into the substantia nigra reticular part. These findings suggest that our stem cell-based orthotopic transplantation approach might contribute to the establishment of regenerative medicine for hypothalamic and pituitary disorders.
  • Mahito Ohkuma, Takuma Maruyama, Toshiyuki Ishii, Nozomi Igarashi, Keiko Azuma, Tatsuya Inoue, Ryo Obata, Ei-ichi Miyachi, Makoto Kaneda
    Oct 25, 2021  
    <title>Abstract</title> Gonadal hormones function as neurosteroids in the retina; however, their targets in the retina have not yet been identified. The present study examined the effects of gonadal hormones on glutamatergic circuits in the retina. Extracellular glutamate concentrations, which correspond to the amount of glutamate released, were monitored using an enzyme-linked fluorescent assay system. Progesterone and pregnenolone both increased extracellular glutamate concentrations at a physiological concentration in pregnancy, whereas estrogen and testosterone did not. Synaptic level observations using a patch clamp technique revealed that progesterone increased the activity of glutamatergic synapses. We also investigated whether high concentrations of gonadal hormones induced changes in the retina during pregnancy. The present results indicate that progesterone activates glutamatergic circuits as a neurosteroid when its concentration is elevated in pregnancy.
  • Naoki Yamamoto, Noriko Hiramatsu, Mahito Ohkuma, Natsuko Hatsusaka, Shun Takeda, Noriaki Nagai, Ei-Ichi Miyachi, Masashi Kondo, Kazuyoshi Imaizumi, Masayuki Horiguchi, Eri Kubo, Hiroshi Sasaki
    Cells, 10(4), Mar 28, 2021  
    Regenerative medicine in ophthalmology that uses induced pluripotent stem cells (iPS) cells has been described, but those studies used iPS cells derived from fibroblasts. Here, we generated iPS cells derived from iris cells that develop from the same inner layer of the optic cup as the retina, to regenerate retinal nerves. We first identified cells positive for p75NTR, a marker of retinal tissue stem and progenitor cells, in human iris tissue. We then reprogrammed the cultured p75NTR-positive iris tissue stem/progenitor (H-iris stem/progenitor) cells to create iris-derived iPS (H-iris iPS) cells for the first time. These cells were positive for iPS cell markers and showed pluripotency to differentiate into three germ layers. When H-iris iPS cells were pre-differentiated into neural stem/progenitor cells, not all cells became positive for neural stem/progenitor and nerve cell markers. When these cells were pre-differentiated into neural stem/progenitor cells, sorted with p75NTR, and used as a medium for differentiating into retinal nerve cells, the cells differentiated into Recoverin-positive cells with electrophysiological functions. In a different medium, H-iris iPS cells differentiated into retinal ganglion cell marker-positive cells with electrophysiological functions. This is the first demonstration of H-iris iPS cells differentiating into retinal neurons that function physiologically as neurons.

Misc.

 69

Professional Memberships

 2

Research Projects

 16

教育内容・方法の工夫(授業評価等を含む)

 7
  • 件名(英語)
    生理学II
    開始年月日(英語)
    2010/05
    終了年月日(英語)
    2016/05
    概要(英語)
    心電図の原理,正常心電図についての講義,骨格筋についての講義
  • 件名(英語)
    生理学実習
    開始年月日(英語)
    2000/05
    終了年月日(英語)
    2015/07
    概要(英語)
    ヒト心電図および血圧について、標準12導出,聴診法による計測実習の指導
  • 件名(英語)
    アセンブリ(生理学研究班)
    開始年月日(英語)
    2001/05
    終了年月日(英語)
    2015/12
    概要(英語)
    生理学に関する導入的な事柄についての講義および実習指導
  • 件名(英語)
    Human Biology
    開始年月日(英語)
    2009/04
    終了年月日(英語)
    2016/11
    概要(英語)
    英文教科書の翻訳,発展学習〜口頭発表を行う、少人数学習形式の講義
  • 件名(英語)
    読書ゼミナール
    開始年月日(英語)
    2009/04
    終了年月日(英語)
    2016/10
    概要(英語)
    和文教科書を基に議論を展開する、少人数学習形式の講義
  • 件名(英語)
    生理学特論実習
    開始年月日(英語)
    2013/04
    終了年月日(英語)
    2017/03
    概要(英語)
    神経生理学に関する研究紹介,議論〜電気生理学の実験指導
  • 件名(英語)
    アセンブリ(少林寺拳法班)
    開始年月日(英語)
    2016/05
    終了年月日(英語)
    2016/12
    概要(英語)
    少林寺拳法の指導補助

その他教育活動上特記すべき事項

 4
  • 件名(英語)
    第1回 医学情報教育ワークショップ参加
    開始年月日(英語)
    2014/07/08
    終了年月日(英語)
    2014/07/08
    概要(英語)
    「eラーニングシステムを体験する -Moodleの基礎-」ワークショップ参加
  • 件名(英語)
    第2回 医学情報教育ワークショップ参加
    開始年月日(英語)
    2015/08/01
    終了年月日(英語)
    2015/08/01
    概要(英語)
    「医学・医療教育におけるインストラクショナルデザインと学習者評価」ワークショップ参加
  • 件名(英語)
    第57回 医学教育ワークショップ参加
    開始年月日(英語)
    2015/09/26
    終了年月日(英語)
    2015/09/26
    概要(英語)
    「プロフェッショナリズムを効果的に教育する」ワークショップ参加
  • 件名(英語)
    第3回 医学情報教育ワークショップ参加
    開始年月日(英語)
    2016/09/16
    終了年月日(英語)
    2016/09/16
    概要(英語)
    「これであなたも教え上手!入門インストラクショナルデザイン」ワークショップ参加