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A fluorescent nanosensor paint reveals the heterogeneity of dopamine release from neurons at individual release sites

Published on bioRxiv - the preprint server for biology
: Elizarova, Sofia; Chouaib, Abed; Shaib, Ali; Mann, Florian; Brose, Nils; Kruss, Sebastian; Daniel, James A.

Volltext ()

2021, 26 S.
European Research Council ERC
Presynaptic Regulatory Principles in Synaptic Plasticity, Neuronal Network Function, and Behaviour
Deutsche Forschungsgemeinschaft DFG
390729940; MBExC
EXC 2067: Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells
Deutsche Forschungsgemeinschaft DFG
390677874; RESOLV
EXC 2033: Ruhr Explores Solvation
Deutsche Forschungsgemeinschaft DFG
Near infrared fluorescent nanomaterials: From photophysics and functional interfaces to biosensors
Preprint, Elektronische Publikation
Fraunhofer IMS ()

The neurotransmitter dopamine is released from discrete axonal structures called varicosities. Its release is essential in behaviour and is critically implicated in prevalent neuropsychiatric diseases. Existing dopamine detection methods are not able to detect and distinguish discrete dopamine release events from multiple varicosities. This prevents an understanding of how dopamine release is regulated across populations of discrete varicosities. Using a near infrared fluorescent (980 nm) dopamine nanosensor ‘paint’ (AndromeDA), we show that action potential-evoked dopamine release is highly heterogeneous across release sites and also requires molecular priming. Using AndromeDA, we visualize dopamine release at up to 100 dopaminergic varicosities simultaneously within a single imaging field with high temporal resolution (15 images/s). We find that ‘hotspots’ of dopamine release are highly heterogeneous and are detected at only ~17% of all varicosities. In neurons lacking Munc13 proteins, which prime synaptic vesicles, dopamine release is abolished during electrical stimulation, demonstrating that dopamine release requires vesicle priming. In summary, AndromeDA reveals the spatiotemporal organization of dopamine release.