Visualizing synaptic dopamine efflux with a 2D composite nanofilm
Chemical neurotransmission constitutes one of the fundamental modalities of communication between neurons. Monitoring release of these chemicals has traditionally been difficult to carry out at spatial and temporal scales relevant to neuron function. To understand chemical neurotransmission more fully, we need to improve the spatial and temporal resolutions of measurements for neurotransmitter release. To address this, we engineered a chemi-sensitive, two-dimensional composite nanofilm that facilitates visualization of the release and diffusion of the neurochemical dopamine with synaptic resolution, quantal sensitivity, and simultaneously from hundreds of release sites. Using this technology, we were able to monitor the spatiotemporal dynamics of dopamine release in dendritic processes, a poorly understood phenomenon. We found that dopamine release is broadcast from a subset of dendritic processes as hotspots that have a mean spatial spread of 3.2 µm (full width at half maximum) and are observed with a mean spatial frequency of 1 hotspot per 7.5 µm of dendritic length. Major dendrites of dopamine neurons and fine dendritic processes, as well as dendritic arbors and dendrites with no apparent varicose morphology participated in dopamine release. Remarkably, these release hotspots colocalized with Bassoon, suggesting that Bassoon may contribute to organizing active zones in dendrites, similar to its role in axon terminals.
All data generated or analyzed during this study are included in the manuscript, supporting file and uploadedvideo files. Source data for this study can be accessed from the following repositories:Figshare: https://figshare.com/articles/figure/DopaFilm_Source_Data/19416875Computer code used in data analysis is available on GitHub at URL noted below:https://github.com/davidackerman/nnmf
Article and author information
Howard Hughes Medical Institute
- Chandima Bulumulla
- Andrew T Krasley
- Ben Cristofori-Armstrong
- William C Valinsky
- Deepika Walpita
- David Ackerman
- David E Clapham
- Abraham G Beyene
Australian Mational Health and Medical Research (APP1162427)
- Ben Cristofori-Armstrong
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Primary rat neuronal culture work was conducted according to the Institutional Animal Care and Use Committee (IACUC) guidelines of Janelia Research Campus of the Howard Hughes Medical Institute.
- Jun Ding, Stanford University, United States
- Preprint posted: January 22, 2022 (view preprint)
- Received: March 18, 2022
- Accepted: July 1, 2022
- Accepted Manuscript published: July 4, 2022 (version 1)
- Version of Record published: August 8, 2022 (version 2)
© 2022, Bulumulla et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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