Real-time three-dimensional tracking of single vesicles reveals abnormal motion and pools of synaptic vesicles in neurons of Huntington's disease mice
Sidong Chen,
Hanna Yoo,
Chun Hei Li,
Chungwon Park,
Gyunam Park,
Li Yang Tan,
Sangyong Jung,
Hyokeun Park
Affiliations
Sidong Chen
Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong
Hanna Yoo
Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong
Chun Hei Li
Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong
Chungwon Park
Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong
Gyunam Park
Creative Research Initiative Center for Chemical Dynamics in Living Cells, Chung-Ang University, Seoul 06974, South Korea; Department of Chemistry, Chung-Ang University, Seoul 06974, South Korea
Li Yang Tan
Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A∗STAR), Singapore; Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
Sangyong Jung
Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A∗STAR), Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
Hyokeun Park
Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong; Department of Physics, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong; State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong; Corresponding author
Summary: Although defective synaptic transmission was suggested to play a role in neurodegenerative diseases, the dynamics and vesicle pools of synaptic vesicles during neurodegeneration remain elusive. Here, we performed real-time three-dimensional tracking of single synaptic vesicles in cortical neurons from a mouse model of Huntington's disease (HD). Vesicles in HD neurons had a larger net displacement and radius of gyration compared with wild-type neurons. Vesicles with high release probability (Pr) were interspersed with low-Pr vesicles in HD neurons, whereas high-Pr vesicles were closer to fusion sites than low-Pr in wild-type neurons. Non-releasing vesicles in HD neurons had an abnormally high prevalence of irregular oscillatory motion. These abnormal dynamics and vesicle pools were rescued by overexpressing Rab11, and the abnormal irregular oscillatory motion was rescued by jasplakinolide. Our studies reveal the abnormal dynamics and pools of synaptic vesicles in the early stages of HD, suggesting a possible pathogenic mechanism of neurodegenerative diseases.
