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

doi:10.1016/j.isci.2021.103181

Real-time three-dimensional tracking of single vesicles reveals abnormal motion and pools of synaptic vesicles in neurons of Huntington's disease mice

iScience. 2021 Sep 28;24(10):103181. doi: 10.1016/j.isci.2021.103181. eCollection 2021 Oct 22.

Authors

Sidong Chen¹, Hanna Yoo¹, Chun Hei Li¹, Chungwon Park¹, Gyunam Park^{2

3}, Li Yang Tan^{4

5}, Sangyong Jung^{4

6}, Hyokeun Park^{1

7

8}

Affiliations

¹ Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
² Creative Research Initiative Center for Chemical Dynamics in Living Cells, Chung-Ang University, Seoul 06974, South Korea.
³ Department of Chemistry, Chung-Ang University, Seoul 06974, South Korea.
⁴ Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A∗STAR), Singapore.
⁵ Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore.
⁶ Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore.
⁷ Department of Physics, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
⁸ State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.

Abstract

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 (P_r) were interspersed with low-P_r vesicles in HD neurons, whereas high-P_r vesicles were closer to fusion sites than low-P_r 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.

Keywords: Biological sciences; Neuroscience; Techniques in neuroscience.