标题：Real-time three-dimensional tracking of single vesicles reveals abnormal motion and pools of synaptic vesicles in neurons of Huntington's disease mice
摘要：SummaryAlthough 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-Prvesicles in HD neurons, whereas high-Prvesicles were closer to fusion sites than low-Prin 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.Graphical abstractDisplay OmittedHighlights•Real-time 3D tracking of single synaptic vesicles in living neurons was performed•3D tracking revealed abnormal motion and pools of releasing vesicles in HD neurons•Non-releasing vesicles in HD neurons showed prevalent irregular oscillatory motion•These abnormalities in HD can be rescued by Rab11 and jasplakinolide respectivelyBiological sciences; Neuroscience; Techniques in neuroscience
