Functional and molecular heterogeneity of D2R neurons along dorsal ventral axis in the striatum

Emma Puighermanal (), Laia Castell, Anna Esteve-Codina, Su Melser, Konstantin Kaganovsky, Charleine Zussy, Jihane Boubaker-Vitre, Marta Gut, Stephanie Rialle, Christoph Kellendonk, Elisenda Sanz, Albert Quintana, Giovanni Marsicano, Miquel Martin, Marcelo Rubinstein, Jean-Antoine Girault, Jun B. Ding and Emmanuel Valjent ()
Additional contact information
Emma Puighermanal: Université Montpellier
Laia Castell: Université Montpellier
Anna Esteve-Codina: Barcelona Institute of Science and Technology
Su Melser: Neurocentre Magendie
Konstantin Kaganovsky: Stanford University School of Medicine
Charleine Zussy: Université Montpellier
Jihane Boubaker-Vitre: Université Montpellier
Marta Gut: Barcelona Institute of Science and Technology
Stephanie Rialle: Université Montpellier
Christoph Kellendonk: Columbia University
Elisenda Sanz: Autonomous University of Barcelona
Albert Quintana: Autonomous University of Barcelona
Giovanni Marsicano: Neurocentre Magendie
Miquel Martin: Université Montpellier
Marcelo Rubinstein: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, CONICET
Jean-Antoine Girault: INSERM UMR-S 1270
Jun B. Ding: Stanford University School of Medicine
Emmanuel Valjent: Université Montpellier

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Action control is a key brain function determining the survival of animals in their environment. In mammals, neurons expressing dopamine D2 receptors (D2R) in the dorsal striatum (DS) and the nucleus accumbens (Acb) jointly but differentially contribute to the fine regulation of movement. However, their region-specific molecular features are presently unknown. By combining RNAseq of striatal D2R neurons and histological analyses, we identified hundreds of novel region-specific molecular markers, which may serve as tools to target selective subpopulations. As a proof of concept, we characterized the molecular identity of a subcircuit defined by WFS1 neurons and evaluated multiple behavioral tasks after its temporally-controlled deletion of D2R. Consequently, conditional D2R knockout mice displayed a significant reduction in digging behavior and an exacerbated hyperlocomotor response to amphetamine. Thus, targeted molecular analyses reveal an unforeseen heterogeneity in D2R-expressing striatal neuronal populations, underlying specific D2R’s functional features in the control of specific motor behaviors.

Date: 2020
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DOI: 10.1038/s41467-020-15716-9

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