Sociability development in mice with cell-specific deletion of the NMDA receptor NR1 subunit gene

Social affiliative behavior is an important component of everyday life in many species and is likely to be disrupted in disabling ways in various neurodevelopmental and neuropsychiatric disorders. Therefore, determining the mechanisms involved in these processes is crucial. A link between N-methyl-d-aspartate (NMDA) receptor function and social behaviors has been clearly established. The cell types in which NMDA receptors are critical for social affiliative behavior, however, remain unclear. Here, we use mice carrying a conditional allele of the NMDA R1 subunit to address this question. Mice bearing a floxed NMDAR1 (NR1) allele were crossed with transgenic calcium/calmodulin-dependent kinase IIα (CaMKIIα)-Cre mice or parvalbumin (PV)-Cre mice targeting postnatal excitatory forebrain or PV-expressing interneurons, respectively, and assessed using the three-chambered Social Approach Test. We found that deletion of NR1 in PV-positive interneurons had no effect on social sniffing, but deletion of NR1 in glutamatergic pyramidal cells resulted in a significant increase in social approach behavior, regardless of age or sex. Therefore, forebrain excitatory neurons expressing NR1 play an important role in regulating social affiliative behavior.