2019 Fiscal Year Research-status Report
Synaptic organizational principles in a subset of brain regions
| Project/Area Number |
18K14842
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | Dendrite / Synapse / Postsynaptic density / Spine / FIB/SEM |
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| Outline of Annual Research Achievements |
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.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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.
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| Strategy for Future Research Activity |
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.
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| Causes of Carryover |
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.
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[Journal Article] a-Synuclein BAC transgenic mice exhibit RBD-like behaviour and hyposmia:a prodromal Parkinson’s disease model2020
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
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Journal Title
BRAIN
Volume: 143
Pages: 249-265
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] GBA haploinsufficiency accelerates alpha-synuclein pathology with altered lipid metabolism in a prodromal model of Parkinson’s disease2019
Author(s)
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
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Journal Title
Human Molecular Genetics
Volume: 28
Pages: 1894-1904
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Cerebellar Neurodegeneration and Neuronal Circuit Remodeling in Golgi pH Regulator-Deficient Mice2019
Author(s)
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
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Journal Title
eNeuro
Volume: 6
Pages: 1-22
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Book] Multiphoton Microscopy2019
Author(s)
Ivar S. Stein, Travis C. Hill, Won Chan Oh, Laxmi K. Parajuli, Karen Zito
Total Pages
21
Publisher
Springer Protocols
ISBN
978-1-4939-9701-5
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[Book] Methods in Molecular Biology2019
Author(s)
Ai Takahashi-Nakazato, Laxmi Kumar Parajuli, Hirohide Iwasaki, Shinji Tanaka, Shigeo Okabe
Total Pages
11
Publisher
Springer Protocols
ISBN
978-1-4939-9076-4
