4.7 Article

Cerebellar dopamine D2 receptors regulate social behaviors

期刊

NATURE NEUROSCIENCE
卷 25, 期 7, 页码 900-+

出版社

NATURE PORTFOLIO
DOI: 10.1038/s41593-022-01092-8

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资金

  1. Inserm
  2. Fondation pour la Recherche Medicale [DEQ20160334919]
  3. La Marato de TV3 Fundacio
  4. ANR EPITRACES [ANR-16-CE16-0018]
  5. ANR DOPAFEAR [ANR-16-CE16-0006]
  6. ANR Bergmann Co [ANR-20-CE37-0024]
  7. Swiss National Science Funds [31003A-175549]
  8. NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation
  9. postdoctoral Labex EpiGenMed fellowship [ANR-10-LABX-12-01]
  10. Marie Curie Intra-European Fellowship [IEF327648]
  11. Beatriu de Pinos fellowship [2017BP00132]
  12. University and Research Grants Management Agency (Government of Catalonia, Spain) [ANR-10-LABX-12-01, RYC2020-029596-I]
  13. Agence Nationale de la Recherche (ANR) [ANR-16-CE16-0006, ANR-16-CE16-0018] Funding Source: Agence Nationale de la Recherche (ANR)
  14. Swiss National Science Foundation (SNF) [31003A_175549] Funding Source: Swiss National Science Foundation (SNF)

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The study demonstrates that the dopamine D2 receptors in cerebellar Purkinje cells play a role in regulating synaptic efficacy and are involved in social behaviors, without affecting motor functions.
The cerebellum, a primary brain structure involved in the control of sensorimotor tasks, also contributes to higher cognitive functions including reward, emotion and social interaction. Although the regulation of these behaviors has been largely ascribed to the monoaminergic system in limbic regions, the contribution of cerebellar dopamine signaling in the modulation of these functions remains largely unknown. By combining cell-type-specific transcriptomics, histological analyses, three-dimensional imaging and patch-clamp recordings, we demonstrate that cerebellar dopamine D2 receptors (D2Rs) in mice are preferentially expressed in Purkinje cells (PCs) and regulate synaptic efficacy onto PCs. Moreover, we found that changes in D2R levels in PCs of male mice during adulthood alter sociability and preference for social novelty without affecting motor functions. Altogether, these findings demonstrate novel roles for D2R in PC function and causally link cerebellar D2R levels of expression to social behaviors. Cutando and colleagues show that changes in D2 dopamine receptor levels in cerebellar Purkinje cells alter sociability and preference for social novelty without affecting motor functions.

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