Dopamine differentially modulates the size of projection neuron ensembles in the intact and dopamine-depleted striatum

  1. Marta Maltese
  2. Jeffrey R March
  3. Alexander G Bashaw
  4. Nicolas X Tritsch  Is a corresponding author
  1. New York University Grossman School of Medicine, United States

Abstract

Dopamine (DA) is a critical modulator of brain circuits that control voluntary movements, but our understanding of its influence on the activity of target neurons in vivo remains limited. Here, we use two-photon Ca2+ imaging to monitor the activity of direct and indirect-pathway spiny projection neurons (SPNs) simultaneously in the striatum of behaving mice during acute and prolonged manipulations of DA signaling. We find that increasing and decreasing DA biases striatal activity towards the direct and indirect pathways, respectively, by changing the overall number of SPNs recruited during behavior in a manner not predicted by existing models of DA function. This modulation is drastically altered in a model of Parkinson's disease. Our results reveal a previously unappreciated population-level influence of DA on striatal output and provide novel insights into the pathophysiology of Parkinson's disease.

Data availability

Source data and code used for analyses are available online (https://github.com/TritschLab).

Article and author information

Author details

  1. Marta Maltese

    Neuroscience and Physiology, New York University Grossman School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jeffrey R March

    Neuroscience and Physiology, New York University Grossman School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Alexander G Bashaw

    Neuroscience and Physiology, New York University Grossman School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Nicolas X Tritsch

    Neuroscience and Physiology, New York University Grossman School of Medicine, New York, United States
    For correspondence
    nicolas.tritsch@nyulangone.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3181-7681

Funding

National Institutes of Health (R00NS087098)

  • Nicolas X Tritsch

National Institutes of Health (DP2NS105553)

  • Nicolas X Tritsch

Alfred P. Sloan Foundation

  • Nicolas X Tritsch

Dana Foundation

  • Nicolas X Tritsch

Whitehall Foundation

  • Nicolas X Tritsch

Leon Levy Foundation

  • Nicolas X Tritsch

Marlene and Paolo Fresco Institute

  • Marta Maltese

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All procedures were carried out according to protocols approved by the NYU Langone Health Institutional Animal Care and Use Committee (protocol #170123).

Reviewing Editor

  1. Nicole Calakos, Duke University Medical Center, United States

Publication history

  1. Received: March 3, 2021
  2. Accepted: May 12, 2021
  3. Accepted Manuscript published: May 13, 2021 (version 1)
  4. Version of Record published: May 28, 2021 (version 2)

Copyright

© 2021, Maltese 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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  1. Marta Maltese
  2. Jeffrey R March
  3. Alexander G Bashaw
  4. Nicolas X Tritsch
(2021)
Dopamine differentially modulates the size of projection neuron ensembles in the intact and dopamine-depleted striatum
eLife 10:e68041.
https://doi.org/10.7554/eLife.68041

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