Studies on the social experience-dependent maturation of parvalbumin-positive interneurons in the mouse orbitofrontal cortex.

Abstract

Cortical areas in the mammalian brain show postnatal maturation at different speeds with various experiences. In particular, maturation of the sensory cortex requires proper sensory experience during the juvenile period, and it accompanies maturation of the parvalbumin-positive inhibitory interneurons (PV+ IN) in the cortex. However, it is still unclear whether PV+ INs also mature and play an important role in the PFC, which matures later than the sensory cortex. Here, we examined maturation of PV+ INs in the subareas of the PFC, the medial prefrontal cortex (mPFC) and the orbitofrontal cortex (OFC), at different developmental ages and according to the sex. Both regions show the maturation of PV+ INs during the postnatal development, and male mice showed significant increase in the PV+ INs during juvenile period while female mice showed significant maturation during adolescent period. Interestingly, post-weaning social isolation (PWSI), deprivation of social-experience during adolescence, impaired maturation of PV+ INs only in the left OFC of the female mice compared with the normal female mice that were group-housed. Furthermore, PWSI female mice showed abnormally increased social behaviors as well as significant reduction in the sniff-induced activities of the left OFC neurons. CRISPR/Cas9 mediated-PV knockdown in the left OFC also induced similar behavioral and physiological changes in female mice. These data demonstrate that maturation of PV+ INs in the left OFC via social-experience is critical for shaping social behaviors in the female mice.