Related Experiment Video
Updated: Jul 29, 2025
Assessing Social Dominance in Mouse Models Using the Tube Test
Published on: June 6, 2025
Balance Between Projecting Neuronal Populations of the Nucleus Accumbens Controls Social Behavior in Mice
Julie Le Merrer1, Bérangère Detraux2, Jorge Gandía3
1Physiologie de la Reproduction et des Comportements, Unité Mixte de Recherche Centre National de la Recherche Scientifique 7247, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement 0085, Institut National de la Santé et de la Recherche Médicale, Université de Tours, Nouzilly, France; iBrain, Unité Mixte de Recherche 1253 Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Faculté des Sciences et Techniques, Université de Tours, Tours, France.
Background:
Deficient social interactions are a hallmark of major neuropsychiatric disorders, and accumulating evidence points to altered social reward and motivation as key underlying mechanisms of these pathologies. In the present study, we further explored the role of the balance of activity between D1 and D2 receptor-expressing striatal projection neurons (D1R- and D2R-SPNs) in the control of social behavior, challenging the hypothesis that excessive D2R-SPN activity, rather than deficient D1R-SPN activity, compromises social behavior.
Methods:
We selectively ablated D1R- and D2R-SPNs using an inducible diphtheria toxin receptor-mediated cell targeting strategy and assessed social behavior as well as repetitive/perseverative behavior, motor function, and anxiety levels. We tested the effects of optogenetic stimulation of D2R-SPNs in the nucleus accumbens (NAc) and pharmacological compounds repressing D2R-SPN.
Results:
Targeted deletion of D1R-SPNs in the NAc blunted social behavior in mice, facilitated motor skill learning, and increased anxiety levels. These behaviors were normalized by pharmacological inhibition of D2R-SPN, which also repressed transcription in the efferent nucleus, the ventral pallidum. Ablation of D1R-SPNs in the dorsal striatum had no impact on social behavior but impaired motor skill learning and decreased anxiety levels. Deletion of D2R-SPNs in the NAc produced motor stereotypies but facilitated social behavior and impaired motor skill learning. We mimicked excessive D2R-SPN activity by optically stimulating D2R-SPNs in the NAc and observed a severe deficit in social interaction that was prevented by D2R-SPN pharmacological inhibition.
Conclusions:
Repressing D2R-SPN activity may represent a promising therapeutic strategy to relieve social deficits in neuropsychiatric disorders.
