Authors
Yuying Liu, Lijiao Cao, Jinger Chen, Junlan Zhou, Chong Huang, Chuqi Li, Xiaoke Nan, Qianhe Dai, Qiqi Yang, Lanqun Mao, Xianchan Li
Published in
Angewandte Chemie (International ed. in English). Pages e6461178. Aug 12, 2026. Epub Aug 12, 2026.
Abstract
Direct single vesicle-resolved quantification of neurotransmitter storage and exocytotic dynamics in an intact living vertebrate nervous system has remained elusive. Here, we establish an in vivo single-vesicle electrochemistry platform in anesthetized living zebrafish larvae, enabling quantification of vesicular dopamine (DA) loading and quantal release dynamics in the intact neural system. By combining intracellular vesicle impact electrochemical cytometry and single-cell amperometry, we directly measure vesicular cargo and exocytotic release in dopaminergic neuron soma of the ventral diencephalon at single-vesicle resolution. Pharmacological validation with a DA elevation drug confirmed the sensitivity and robustness of the approach. Application of this platform to a chemical-induced Parkinsonian model revealed pronounced reductions in vesicular DA content, altered release patterns, and impaired exocytotic dynamics. Rasagiline treatment partially restored vesicular DA storage and release dynamics toward physiological levels, suggesting a protective modulation of vesicle function. This in vivo electrochemical method offers a single vesicle-resolved analytical platform for dissecting vesicular heterogeneity and dysfunction directly in intact neural systems, thereby bridging single-vesicle chemistry with in vivo neurobiology and opening new avenues for mechanistic studies of neurodegeneration and therapeutic intervention.
PMID:
42585093
Bibliographic data and abstract were imported from PubMed on 13 Aug 2026.
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