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The oxytocin receptor (OTR) plays critical roles in social behavior development. Despite its significance, brain-wide quantitative understanding of OTR expression remains limited in postnatally developing brains. Here, we develop postnatal 3D template brains to register whole brain images with cellular resolution to systematically quantify OTR cell densities. We utilize fluorescent reporter mice (Otr venus/+ ) and find that cortical regions show temporally and spatially heterogeneous patterns with transient postnatal OTR expression without cell death. Cortical OTR cells are largely glutamatergic neurons with the exception of cells in layer 6b. Subcortical regions show similar temporal regulation except the hypothalamus and two hypothalamic nuclei display sexually dimorphic OTR expression. Lack of OTR expression correlates with reduced dendritic spine densities in selected cortical regions of developing brains. Lastly, we create a website to visualize our high-resolution imaging data. In summary, our research provides a comprehensive resource for postnatal OTR expression in the mouse brain.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired communication, difficulty in companionship, repetitive behaviors and restricted interests. Recent studies have shown amelioration of ASD symptoms by intranasal administration of oxytocin and demonstrated the association of polymorphisms in the oxytocin receptor (Oxtr) gene with ASD patients. Deficient pruning of synapses by microglial cells in the brain has been proposed as potential mechanism of ASD. Other researchers have shown specific activation of microglial cells in brain regions related to sociality in patients with ASD. Although the roles of Oxtr and microglia in ASD are in the spotlight, the relationship between them remains to be elucidated. In this study, we found abnormal activation of microglial cells and a reduction of postsynaptic density protein PSD95 expression in the Oxtr-deficient brain. Moreover, pharmacological inhibition of microglia during development can alter the expression of PSD95 and ameliorate abnormal mother-infant communication in Oxtr-deficient mice. Our results suggest that microglial abnormality is a potential mechanism of the development of Oxt/Oxtr mediated ASD-like phenotypes., (Copyright © 2016 Elsevier Inc. All rights reserved.)