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2019 年度 実施状況報告書

電顕三次元立体再構築に基づく脳の様々な領域におけるシナプス結合の共通原理の解明

研究課題

研究課題/領域番号 18K14842
研究機関順天堂大学

研究代表者

パラジュリ ラクシミ・クマール  順天堂大学, 医学部, 助教 (10812448)

研究期間 (年度) 2018-04-01 – 2021-03-31
キーワードDendrite / Synapse / Postsynaptic density / Spine / FIB/SEM
研究実績の概要

We revealed that the organizational principle of dendritic spines differs according to the regions of the brain. For example, in CA1 proximal stratum radiatum, cortex and cerebellum we revealed that the total area of the postsynaptic density increases linearly with dendritic diameter. However, similar trend was not observed for the dendrites in striatum and stratum lacunosum moleculare. Glutamate uncaging experiment revealed that neck length is more influential than head volume in determining the magnitude of voltage change at the soma in the CA1 proximal radiatum.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

We were able to obtain new data regarding the scaling of the total synaptic content(the area of the postsynaptic density) in the dendrites with the dendritic diameter. In addition, we found that the ratio of PSD area to neck length was not correlated with dendritic diameter and were rather similar between dendrites of different diameters. In addition to the FIB/SEM data, we have also incorporated glutamate uncaging data in this experiment regarding the influence of spine head and spine neck in the determining the magnitude of voltage change at the soma.
The proposed experiments progressed smoothly and the scientific content and the findings of this study is novel. Currently I am working a manuscript for this project to be submitted to scientific journals.

今後の研究の推進方策

At present I am writing a manuscript compiling the data of this research. The major findings of this project and the storyline of the manuscript is clear. The study so far focused on the organization of dendritic spines in wild-type mouse. Currently the analysis of dendritic spine structure in the disease mouse model is also underway to see how the dendritic spine structure changes in pathological conditions. Moreover, in future, in addition to observing the morphology of dendritic spines I am also interested to study the organization of intracellular structures such as endoplasmic reticulum and Mitochondria in the dendrites and spines both in the wild-type and mutant mouse. Also, I am interested to analyze if the axon-coupled spines are the structural features of engram , memory spines.

次年度使用額が生じた理由

In this project, during the course of experiment and data analysis we encountered some new data concerning the relationship between dendritic diameter and the synapse content. Furthermore, we also found out that the spine morphology is altered in Parkinson`s model mouse. Although the analysis is near to completion we would like to examine this issue in more detail. For this reason, there was some remaining amount of grant this year and not all the money was used up in the previous fiscal year. The remaining amount of money will be used for additional data analysis.

  • 研究成果

    (7件)

すべて 2020 2019

すべて 雑誌論文 (3件) (うち国際共著 3件、 査読あり 3件、 オープンアクセス 2件) 学会発表 (2件) 図書 (2件)

  • [雑誌論文] a-Synuclein BAC transgenic mice exhibit RBD-like behaviour and hyposmia:a prodromal Parkinson’s disease model2020

    • 著者名/発表者名
      Taguchi T, Ikuno M, Hondo M, Parajuli LK, Taguchi K, Ueda J, Sawamura M, Okuda S, Nakanishi E, Hara J, Uemura N, Hatanaka Y, Ayaki T, Matsuzawa S, Tanaka M, El-Agnaf OMA, Koike M, Yanagisawa M, Uemura MT, Yamakado H, Takahashi R
    • 雑誌名

      BRAIN

      巻: 143 ページ: 249-265

    • DOI

      doi:10.1093/brain/awz380

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] GBA haploinsufficiency accelerates alpha-synuclein pathology with altered lipid metabolism in a prodromal model of Parkinson’s disease2019

    • 著者名/発表者名
      Masashi Ikuno, Hodaka Yamakado, Hisako Akiyama, Laxmi Kumar Parajuli, Katsutoshi Taguchi, Junko Hara, Norihito Uemura, Yusuke Hatanaka, Katsumi Higaki, Kousaku Ohno, Masaki Tanaka, Masato Koike, Yoshio Hirabayashi, Ryosuke Takahashi
    • 雑誌名

      Human Molecular Genetics

      巻: 28 ページ: 1894-1904

    • DOI

      doi: 10.1093/hmg/ddz030

    • 査読あり / 国際共著
  • [雑誌論文] Cerebellar Neurodegeneration and Neuronal Circuit Remodeling in Golgi pH Regulator-Deficient Mice2019

    • 著者名/発表者名
      Yu-shin Sou, Soichiro Kakuta, Yuji Kamikubo, Kazue Niisato, Takashi Sakurai, Laxmi Kumar Parajuli, Isei Tanida, Hiromitsu Saito, Noboru Suzuki, Kenji Sakimura, Yusuke Maeda, Taroh Kinoshita, Yasuo Uchiyama and Masato Koike
    • 雑誌名

      eNeuro

      巻: 6 ページ: 1-22

    • DOI

      doi: 10.1523/ENEURO.0427-18.2019.

    • 査読あり / オープンアクセス / 国際共著
  • [学会発表] Developmental changes of spine morphology in the striatum and its alteration in Parkinson`s disease mouse model2020

    • 著者名/発表者名
      Parajuli Kumar Laxmi, Wako Ken, Maruo Suiki, Takahashi Ryosuke, Koike Masato
    • 学会等名
      ABiS Symposium Okazaki
  • [学会発表] Distinct age-dependent subcellular changes in a model mouse of Parkinson's disease as revealed by volumetric FIB/SEM imaging of striatum2019

    • 著者名/発表者名
      Parajuli Kumar Laxmi, Wako Ken, Maruo Suiki, Takahashi Ryosuke, Koike Masato
    • 学会等名
      42nd Annual Meeting of the Japanese Neuroscience Society
  • [図書] Multiphoton Microscopy2019

    • 著者名/発表者名
      Ivar S. Stein, Travis C. Hill, Won Chan Oh, Laxmi K. Parajuli, Karen Zito
    • 総ページ数
      21
    • 出版者
      Springer Protocols
    • ISBN
      978-1-4939-9701-5
  • [図書] Methods in Molecular Biology2019

    • 著者名/発表者名
      Ai Takahashi-Nakazato, Laxmi Kumar Parajuli, Hirohide Iwasaki, Shinji Tanaka, Shigeo Okabe
    • 総ページ数
      11
    • 出版者
      Springer Protocols
    • ISBN
      978-1-4939-9076-4

URL: 

公開日: 2021-01-27  

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