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

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Listed:
  • Benoît Delignat-Lavaud

    (Université de Montréal
    Université de Montréal
    Université de Montréal)

  • Jana Kano

    (Université de Montréal
    Université de Montréal
    Université de Montréal)

  • Charles Ducrot

    (Université de Montréal
    Université de Montréal
    Université de Montréal)

  • Ian Massé

    (Université de Montréal)

  • Sriparna Mukherjee

    (Université de Montréal
    Université de Montréal
    Université de Montréal
    Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network)

  • Nicolas Giguère

    (Université de Montréal
    Université de Montréal
    Université de Montréal)

  • Luc Moquin

    (McGill University)

  • Catherine Lévesque

    (Université de Montréal)

  • Samuel Burke

    (Université de Montréal
    Université de Montréal
    Université de Montréal)

  • Raphaëlle Denis

    (Université de Montréal
    Université de Montréal
    Université de Montréal)

  • Marie-Josée Bourque

    (Université de Montréal
    Université de Montréal
    Université de Montréal
    Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network)

  • Alex Tchung

    (Université de Montréal
    Université de Montréal
    Université de Montréal)

  • Pedro Rosa-Neto

    (McGill University)

  • Daniel Lévesque

    (Université de Montréal)

  • Louis Beaumont

    (Université de Montréal)

  • Louis-Éric Trudeau

    (Université de Montréal
    Université de Montréal
    Université de Montréal
    Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network)

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.

Suggested Citation

  • 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 T, 2023. "Synaptotagmin-1-dependent phasic axonal dopamine release is dispensable for basic motor behaviors in mice," Nature Communications, Nature, vol. 14(1), pages 1-24, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39805-7
    DOI: 10.1038/s41467-023-39805-7
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    References listed on IDEAS

    as
    1. Changhe Wang & Xinjiang Kang & Li Zhou & Zuying Chai & Qihui Wu & Rong Huang & Huadong Xu & Meiqin Hu & Xiaoxuan Sun & Suhua Sun & Jie Li & Ruiying Jiao & Panli Zuo & Lianghong Zheng & Zhenyu Yue & Zh, 2018. "Synaptotagmin-11 is a critical mediator of parkin-linked neurotoxicity and Parkinson’s disease-like pathology," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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    Cited by:

    1. Marie A. Labouesse & Maria Wilhelm & Zacharoula Kagiampaki & Andrew G. Yee & Raphaelle Denis & Masaya Harada & Andrea Gresch & Alina-Măriuca Marinescu & Kanako Otomo & Sebastiano Curreli & Laia Serrat, 2024. "A chemogenetic approach for dopamine imaging with tunable sensitivity," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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