1Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada;
2Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada;
3SNC and CIRCA Research Groups, Université de Montréal, Montréal, Québec, Canada;
4Hôpital du Sacré-Cœur-de-Montréal, CIUSSS NIM, Université de Montréal, Montreal, Québec, Canada;
5Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815;
6Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Québec, Canada;
7Faculty of Pharmacy, Université de Montréal, Montreal, Québec, Canada
Collection Citation: Benoît elignat-Lavaud, Jana Kano, Charles Ducrot, Ian Massé, Sriparna Mukherjee, Nicolas Giguère, Luc Moquin, Catherine Lévesque, Samuel Burke, Raphaëlle enis, Marie-Josée ourque, Alex Tchung, Pedro Rosa-Neto, Daniel Lévesque, Louis De Beaumont, louis-eric.trudeau 2023. Protocols for "Synaptotagmin-1-dependent phasic axonal dopamine release is dispensable for basic motor behaviors in mice". protocols.io https://dx.doi.org/10.17504/protocols.io.n92ldpoj8l5b/v1
Manuscript citation:
Delignat-Lavaud, B., Kano, J., Ducrot, C. et al. Synaptotagmin-1-dependent phasic axonal dopamine release is dispensable for basic motor behaviors in mice. Nat Commun14, 4120 (2023). https://doi.org/10.1038/s41467-023-39805-7
License: This is an open access collection distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Protocol status: Working
We use this collection and it's working
Created: May 31, 2023
Last Modified: May 31, 2024
Collection Integer ID: 82711
Keywords: ASAPCRN, dependent phasic axonal dopamine release, dependent axonal da release in the striatum, basal extracellular da levels in the striatum, dependent axonal da release, basal tone of extracellular da, da neuron, parkinson, motor dysfunctions in pd, extracellular da level, extensive loss of da innervation, extracellular da, syt1 ckoda mice, diffuse basal tone of da, dependent motor task, neuron, conditional deletion of the calcium sensor, dependent da release, abolition of phasic da release, da innervation, dispensable for basic motor behavior, many motor behavior, dependent motor functions in the context
Abstract
In Parkinson’s disease (PD), motor dysfunctions only become apparent after extensive loss of DA innervation. This resilience has been hypothesized to be due to the ability of many motor behaviors to be sustained through a diffuse basal tone of DA; but experimental evidence for this is limited. Here we show that conditional deletion of the calcium sensor synaptotagmin-1 (Syt1) in DA neurons (Syt1 cKODA mice) abrogates most activity-dependent axonal DA release in the striatum and mesencephalon, leaving somatodendritic (STD) DA release intact. Strikingly, Syt1 cKODAmice showed intact performance in multiple unconditioned DA-dependent motor tasks and even in a task evaluating conditioned motivation for food. Considering that basal extracellular DA levels in the striatum were unchanged, our findings suggest that activity-dependent DA release is dispensable for such tasks and that they can be sustained by a basal tone of extracellular DA. Taken together, our findings reveal the striking resilience of DA-dependent motor functions in the context of a near-abolition of phasic DA release, shedding new light on why extensive loss of DA innervation is required to reveal motor dysfunctions in PD.
