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