Functional and molecular heterogeneity of D2R neurons along dorsal ventral axis in the striatum
Nat Commun. 2020-04-23; 11(1):
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Puighermanal E(1)(2), Castell L(3), Esteve-Codina A(4), Melser S(5)(6), Kaganovsky K(7), Zussy C(3), Boubaker-Vitre J(3), Gut M(4)(8), Rialle S(3), Kellendonk C(9)(10), Sanz E(11), Quintana A(11), Marsicano G(5)(6), Martin M(3), Rubinstein M(12)(13)(14), Girault JA(15)(16)(17), Ding JB(7), Valjent E(18).
(1)IGF, CNRS, INSERM, Université Montpellier, Montpellier, France. .
(2)Neuroscience Institute, Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona, Bellaterra, Spain. .
(3)IGF, CNRS, INSERM, Université Montpellier, Montpellier, France.
(4)Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08028, Barcelona, Spain.
(5)INSERM U1215, Neurocentre Magendie, Bordeaux, France.
(6)Neurocentre Magendie, Université de Bordeaux, Bordeaux, France.
(7)Department of Neurosurgery and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
(8)Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003, Barcelona, Spain.
(9)Departement of Psychology and Pharmacology, Columbia University, New York, NY, USA.
(10)Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA.
(11)Neuroscience Institute, Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona, Bellaterra, Spain.
(12)Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, CONICET, Buenos Aires, Argentina.
(13)FCEN, Universidad de Buenos Aires, Buenos Aires, Argentina.
(14)Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
(15)INSERM UMR-S 1270, Paris, France.
(16)Faculty of Sciences, Sorbonne University, Paris, France.
(17)Institut du Fer à Moulin, Paris, France.
(18)IGF, CNRS, INSERM, Université Montpellier, Montpellier, France. .
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.