Synaptotagmin-1-dependent phasic axonal dopamine release is dispensable for basic motor behaviors in mice

Benoît Delignat-Lavaud, Jana Kano, Charles Ducrot, Ian Massé, Sriparna Mukherjee, Nicolas Giguère, Luc Moquin, Catherine Lévesque, Samuel Burke, Raphaëlle Denis, Marie-Josée Bourque, Alex Tchung, Pedro Rosa-Neto, Daniel Lévesque, Louis Beaumont and Louis-Éric Trudeau ()
Additional contact information
Benoît Delignat-Lavaud: Université de Montréal
Jana Kano: Université de Montréal
Charles Ducrot: Université de Montréal
Ian Massé: Université de Montréal
Sriparna Mukherjee: Université de Montréal
Nicolas Giguère: Université de Montréal
Luc Moquin: McGill University
Catherine Lévesque: Université de Montréal
Samuel Burke: Université de Montréal
Raphaëlle Denis: Université de Montréal
Marie-Josée Bourque: Université de Montréal
Alex Tchung: Université de Montréal
Pedro Rosa-Neto: McGill University
Daniel Lévesque: Université de Montréal
Louis Beaumont: Université de Montréal
Louis-Éric Trudeau: Université de Montréal

Nature Communications, 2023, vol. 14, issue 1, 1-24

Abstract: 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 cKODA mice 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.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39805-7

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DOI: 10.1038/s41467-023-39805-7

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