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

Elizarova, S., Chouaib, A. A., Shaib, A. H., Hill, B., Mann, F., Brose, N., et al. (2022). A fluorescent nanosensor paint detects dopamine release at axonal varicosities with high spatiotemporal resolution. Proceedings of the National Academy of Sciences of the United States of America, 119(22): e2202842119. doi:10.1073/pnas.2202842119.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000B-2B02-3 Version Permalink: https://hdl.handle.net/21.11116/0000-000B-50BE-5
Genre: Journal Article

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 Creators:
Elizarova, Sofia1, Author           
Chouaib, Abed Alrahman, Author
Shaib, Ali H.1, Author           
Hill, Björn, Author
Mann, Florian, Author
Brose, Nils1, Author           
Kruss, Sebastian, Author
Daniel, James1, Author           
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350300              

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 Abstract: 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 ∼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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Language(s): eng - English
 Dates: 2022-05-25
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1073/pnas.2202842119
 Degree: -

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Project name : We thank H. Taschenberger, N. Lipstein, P. Robinson, S. Rizzoli, J. Heathers, A. Sigler, F. Benseler, M. Cousin, P. Kaeser, and members of the Janshoff laboratory for their essential insights regarding neuron culture, data analysis, and experimental procedures. We thank C. Imig, N. Lipstein, F. Benseler, and the DNA Core Facility of the Max Planck Institute for Multidisciplinary Sciences for their assistance with the maintenance of the various mouse lines used here. We thank P. Lingor, K. Kobayashi, and Riken for providing us with the TH-EGFP mouse line. We thank A. Spreinat and C. Geisler for help with the imaging system. This work was funded by the European Commission (ERC Advanced Grant SynPrime to N.B.) and the Deutsche Forschungsgemeinschaft (DFG) grant under Germany’s Excellence Strategy (EXC 2067/1-390729940 to N.B. and EXC 2033-390677874-RESOLV to S.K.). We thank the DFG for funding (KR 4242/7-1) and support via the Heisenberg Programme (to S.K.)
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Funding organization : -
Project name : Presynaptic Regulatory Principles in Synaptic Plasticity, Neuronal Network Function, and Behaviour - SynPrime
Grant ID : 670283
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)

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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : PNAS
  Other : Proceedings of the National Academy of Sciences of the USA
  Abbreviation : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
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Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: - Volume / Issue: 119 (22) Sequence Number: e2202842119 Start / End Page: - Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230