Synaptic organizational principles in a subset of brain regions

• Project/Area Number: 18K14842
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46020:Anatomy and histopathology of nervous system-related
• Research Institution: Juntendo University
• Principal Investigator: Parajuli Laxmi Kumar 順天堂大学, 医学部, 助教 (10812448)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: pine / Synapse / Dendrite / Parkinson's disease / Spine / FIB/SEM / interpeduncular nucleus / Postsynaptic density / Dendritic Spine / Synapses / Synaptic organisation / Neuronal circuit

Outline of Final Research Achievements

My research used three-dimensional electron microscopy to reveal the structures of neuronal compartments in different areas of the brain. I revealed the unique structures of neuronal dendrites and the placement of dendritic spines along the neuronal dendrites. Furthermore, in the striatum, I studied the developmental changes of dendritic spine morphology in 1, 3, 6 and 22 months of age in the normal mice and in the mouse model of Parkinson’s disease. I found that the spine density decreases, but the average head volume increases with age in wild-type mice. However, the increase in spine head volume with age was not seen in Parkinson’s disease mouse model. In summary, my research revealed the structure of dendritic spines in the hippocampus, cerebral cortex, striatum, cerebellum and the unique dendritic protrusion in the interpeduncular nucleus of wild-type mice; and the abnormality in the structures of dendritic spines in the striatum of Parkinson’s disease mouse model.

Academic Significance and Societal Importance of the Research Achievements

本研究で、海馬、皮質、小脳では、樹状突起の直径とともに脊椎密度が増加することが明らかにした。 さらに、正常な野生型マウスの線条体で見られた平均脊椎頭部体積の年齢による増加はパーキンソン病のモデルマウスでは観察されなかった。

Research Products

• [Int'l Joint Research] Max Planck Florida Research Institute/University of Colorado/Johns Hopkins School of Medicine(米国)
• [Journal Article] Geometry and the Organizational Principle of Spine Synapses along a Dendrite (2020)
  • Author(s): Parajuli Laxmi Kumar、Urakubo Hidetoshi、Takahashi-Nakazato Ai、Ogelman Roberto、Iwasaki Hirohide、Koike Masato、Kwon Hyung-Bae、Ishii Shin、Oh Won Chan、Fukazawa Yugo、Okabe Shigeo
  • Journal Title: eneuro Volume: 7 Issue: 6 Pages: 0248-20
  • DOI: 10.1523/eneuro.0248-20.2020
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] a-Synuclein BAC transgenic mice exhibit RBD-like behaviour and hyposmia:a prodromal Parkinson’s disease model (2020)
  • Author(s): 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
  • Journal Title: BRAIN Volume: 143 Issue: 1 Pages: 249-265
  • DOI: 10.1093/brain/awz380
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] GBA haploinsufficiency accelerates alpha-synuclein pathology with altered lipid metabolism in a prodromal model of Parkinson’s disease (2019)
  • Author(s): Ikuno Masashi、Yamakado Hodaka、Akiyama Hisako、Parajuli Laxmi Kumar、Taguchi Katsutoshi、Hara Junko、Uemura Norihito、Hatanaka Yusuke、Higaki Katsumi、Ohno Kousaku、Tanaka Masaki、Koike Masato、Hirabayashi Yoshio、Takahashi Ryosuke
  • Journal Title: Human Molecular Genetics Volume: 印刷中 Issue: 11 Pages: 1894-1904
  • DOI: 10.1093/hmg/ddz030
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cerebellar Neurodegeneration and Neuronal Circuit Remodeling in Golgi pH Regulator-Deficient Mice (2019)
  • Author(s): Sou Yu-shin、Kakuta Soichiro、Kamikubo Yuji、Niisato Kazue、Sakurai Takashi、Parajuli Laxmi Kumar、Tanida Isei、Saito Hiromitsu、Suzuki Noboru、Sakimura Kenji、Maeda Yusuke、Kinoshita Taroh、Uchiyama Yasuo、Koike Masato
  • Journal Title: eNeuro Volume: 6 Issue: 3 Pages: 0427-18
  • DOI: 10.1523/eneuro.0427-18.2019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Technical Toolbox for Decoding Synaptic Complexity (2018)
  • Author(s): Parajuli LK
  • Journal Title: Juntendo Medical Journal Volume: 64 Issue: 5 Pages: 386-391
  • DOI: 10.14789/jmj.2018.64.JMJ18-LN03
  • NAID: 130007535581
  • ISSN: 2187-9737, 2188-2126
  • Peer Reviewed / Open Access
• [Journal Article] Near-infrared deep brain stimulation via upconversion nanoparticle-mediated optogenetics. (2018)
  • Author(s): Chen S, Weitemier AZ, Zeng X, He L, Wang X, Tao Y, Huang AJY, Hashimotodani Y, Kano M, Iwasaki H, Parajuli LK, Okabe S, Teh DBL, All AH, Tsutsui-Kimura I, Tanaka KF, Liu X, McHugh TJ.
  • Journal Title: Science Volume: 359 Issue: 6376 Pages: 679-684
  • DOI: 10.1126/science.aaq1144
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Kv2 Ion Channels Determine the Expression and Localization of the Associated AMIGO-1 Cell Adhesion Molecule in Adult Brain Neurons (2018)
  • Author(s): Bishop Hannah I.、Cobb Melanie M.、Kirmiz Michael、Parajuli Laxmi K.、Mandikian Danielle、Philp Ashleigh M.、Melnik Mikhail、Kuja-Panula Juha、Rauvala Heikki、Shigemoto Ryuichi、Murray Karl D.、Trimmer James S.
  • Journal Title: Front Mol Neurosci. Volume: 11
  • DOI: 10.3389/fnmol.2018.00001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Unique synaptic topography of crest-type synapses in the interpeduncular nucleus. (2020)
  • Author(s): Laxmi Kumar Parajuli, Masato Koike
  • Organizer: 日本解剖学会第108回関東支部学術集会
• [Presentation] Developmental changes of spine morphology in the striatum and its alteration in Parkinson`s disease mouse model (2020)
  • Author(s): Parajuli Kumar Laxmi, Wako Ken, Maruo Suiki, Takahashi Ryosuke, Koike Masato
  • Organizer: ABiS Symposium Okazaki
• [Presentation] Distinct age-dependent subcellular changes in a model mouse of Parkinson's disease as revealed by volumetric FIB/SEM imaging of striatum (2019)
  • Author(s): Parajuli Kumar Laxmi, Wako Ken, Maruo Suiki, Takahashi Ryosuke, Koike Masato
  • Organizer: 42nd Annual Meeting of the Japanese Neuroscience Society
• [Book] Multiphoton Microscopy (2019)
  • Author(s): Ivar S. Stein, Travis C. Hill, Won Chan Oh, Laxmi K. Parajuli, Karen Zito
  • Total Pages: 21
  • Publisher: Springer Protocols
  • ISBN: 9781493997015
• [Book] Methods in Molecular Biology (2019)
  • Author(s): Ai Takahashi-Nakazato, Laxmi Kumar Parajuli, Hirohide Iwasaki, Shinji Tanaka, Shigeo Okabe
  • Total Pages: 11
  • Publisher: Springer Protocols
  • ISBN: 9781493990764