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Publication : A fluorescent nanosensor paint detects dopamine release at axonal varicosities with high spatiotemporal resolution.

First Author  Elizarova S Year  2022
Journal  Proc Natl Acad Sci U S A Volume  119
Issue  22 Pages  e2202842119
PubMed ID  35613050 Mgi Jnum  J:331373
Mgi Id  MGI:7388109 Doi  10.1073/pnas.2202842119
Citation  Elizarova S, et al. (2022) A fluorescent nanosensor paint detects dopamine release at axonal varicosities with high spatiotemporal resolution. Proc Natl Acad Sci U S A 119(22):e2202842119
abstractText  The neurotransmitter dopamine (DA) controls multiple behaviors and is perturbed in several major brain diseases. DA is released from large populations of specialized structures called axon varicosities. Determining the DA release mechanisms at such varicosities is essential for a detailed understanding of DA biology and pathobiology but has been limited by the low spatial resolution of DA detection methods. We used a near-infrared fluorescent DA nanosensor paint, adsorbed nanosensors detecting release of dopamine (AndromeDA), to detect DA secretion from cultured murine dopaminergic neurons with high spatial and temporal resolution. We found that AndromeDA detects discrete DA release events and extracellular DA diffusion and observed that DA release varies across varicosities. To systematically detect DA release hotspots, we developed a machine learning-based analysis tool. AndromeDA permitted the simultaneous visualization of DA release for up to 100 dopaminergic varicosities, showing that DA release hotspots are heterogeneous and occur at only approximately 17% of all varicosities, indicating that many varicosities are functionally silent. Using AndromeDA, we determined that DA release requires Munc13-type vesicle priming proteins, validating the utility of AndromeDA as a tool to study the molecular and cellular mechanism of DA secretion.
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