Synaptotagmin-1 is the Ca2+ sensor for fast striatal dopamine release
- Harvard Medical School, United States
Abstract
Dopamine powerfully controls neural circuits through neuromodulation. In the vertebrate striatum, dopamine adjusts cellular functions to regulate behaviors across broad time scales, but how the dopamine secretory system is built to support fast and slow neuromodulation is not known. Here, we set out to identify Ca2+-triggering mechanisms for dopamine release. We find that synchronous dopamine secretion is abolished in acute brain slices of conditional knockout mice in which Synaptotagmin-1 is removed from dopamine neurons. This indicates that Synaptotagmin-1 is the Ca2+ sensor for fast dopamine release. Remarkably, dopamine release induced by strong depolarization and asynchronous release during stimulus trains are unaffected by Synaptotagmin-1 knockout. Microdialysis further reveals that these modes and action potential-independent release provide significant amounts of extracellular dopamine in vivo. We propose that the molecular machinery for dopamine secretion has evolved to support fast and slow signaling modes, with fast release requiring the Ca2+ sensor Synaptotagmin-1.
Data availability
All data generated in the study are included in the figures, including individual data points.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (R01NS103484)
- Pascal S Kaeser
Harvard Medical School (Dean's Initiative Award)
- Pascal S Kaeser
Harvard University (Harvard-MIT Joint research grant)
- Pascal S Kaeser
Harvard Medical School (Hearst Fellowship)
- Aditi Banerjee
Harvard Medical School (Brooks Fellowship)
- Aditi Banerjee
Harvard Medical School (Gordon Fellowship)
- Changliang Liu
Marshallplan-Jubiläumsstiftung (Exchange Scholarship)
- Paulina Nemcova
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Lu Chen, Stanford University, United States
Ethics
Animal experimentation: All animal experiments were performed according to institutional guidelines of Harvard University, and were in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The animals were handled according to protocols (protocol number IS00000049) approved by the institutional animal care and use committee (IACUC).
Version history
- Received: April 28, 2020
- Accepted: June 2, 2020
- Accepted Manuscript published: June 3, 2020 (version 1)
- Version of Record published: June 26, 2020 (version 2)
Copyright
© 2020, Banerjee 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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Synaptotagmin-1 is the Ca2+ sensor for fast striatal dopamine release
eLife 9:e58359.
https://doi.org/10.7554/eLife.58359
