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

Abstract

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 PVexpressing 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.

Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice

“…Previous studies on parvalbumin (Pv)-positive neurons, a major GABAergic neuron type 24 , reported key roles of Pv neurons in the regulation of social cognition and behaviors 21,25,26 . Currently, whether and how the abovementioned ASD-related NMDAR dysfunctions are associated with GABA or Pv neuronal dysfunctions and social deficits have remained largely obscure [27][28][29][30] .…”

Excess neonatal testosterone causes male-specific social and fear memory deficits in wild-type mice

“…Notably, neonatal testosterone treatment did not affect litter size, pup mortality, or sex distribution (data not shown). Additionally, veh-treated mice exhibited behavior statistically equivalent to that of mice that were undisturbed as neonates (no neonatal injection); both social preference indices at ~PN30 and 24 hr fear memory results at ~PN60 were comparable between mice administered veh and never-injected control mice we have collected over various experiments (54)(55)(56)(57). However, there are several caveats to consider, including possible effects of neonatal injections on maternal care, which could in turn affect pup behavior (44,58).…”

Maturation of Nucleus Accumbens Synaptic Transmission Signals a Critical Period for the Rescue of Social Deficits in a Mouse Model of Autism Spectrum Disorder

“…Our data delineate the maturation of spontaneous synaptic transmission in the NAc shell across early postnatal development, uncovering distinct early maturation signatures between C57BL/6J and BTBR mice, strains that display distinct patterns of NAc-mediated social behavior. These synaptic changes coincide with key developmental changes in social communication, play, affiliative and social approach behavior [154][155][156][157][158] , and abridge a period in which environmental conditions and stress bear a disproportionate impact in shaping future social behavior [159][160][161][162][163] . Accordingly, we revealed a restricted time window for the rescue of social interaction deficits in BTBR mice by rapamycin treatment.…”