To selectively ascertain a role for OXTR in the adult brain, Lee et al generated a floxed Oxtr mouse, which has been used to delete Oxtr from selective brain areas in the adult by introduction of a cell type specific Cre recombinase ( Lee et al., 2008a, b Macbeth et al., 2009 Pagani et al., 2011). The possibility also exists that congenital OXTR loss throughout mouse development makes a significant contribution to reported disruption of adult behaviors, as has been shown for the serotonin (5-HT) 1a receptor ( Gross et al., 2002). For example, the septum, the hippocampus, the amygdala, and the piriform cortex have all been implicated. Hypotheses of the underlying mechanisms that generate these behavioral phenotypes in mutant mice, in which target genes are deleted constitutively from all tissues, have been informed mostly by our understanding of OXTR ligand binding distribution in the adult mouse brain. Maternal care is partially impaired in both lines of mice ( Takayanagi et al., 2005 Pedersen et al., 2006). ![]() In addition, the adult Oxtr KO mouse is seizure-prone and has poor reversal learning, a laboratory proxy of poor cognitive flexibility ( Sala et al., 2011). OXTR signaling seems to play more of role in intrastrain social recognition, which is a more difficult perceptual and memory task than interstrain social recognition ( Macbeth et al., 2009). Similarly, adult OXT receptor ( Oxtr) knock-out mice also display evidence of poor social recognition behavior ( Takayanagi et al., 2005 Lee et al., 2008a Macbeth et al., 2009). In mice in which Oxt has been constitutively deleted, adults exhibit poor social recognition behavior ( Ferguson et al., 2000 Macbeth et al., 2009). In humans, whereas data from genetic association studies are difficult to replicate ( Bakermans-Kranenburg and van Ijzendoorn, 2013), results from studies with intranasal treatment with OXT are consistent with a role for OXT in adult human social behavior ( Guastella and Macleod, 2012). There is substantial experimental evidence in humans and pre-clinical models that oxytocin (OXT) plays a role in adult behavior. OXTR are also identified in several tissues in the whole late embryo, including the adrenal glands, brown adipose tissue, and the oronasal cavity. Summary: Quantitative mapping of selective OXTR ligand binding during postnatal development in the mouse reveals an unexpected, transient expression in layers II/III throughout the mouse neocortex. We discuss our findings in the context of developmental disorders (including autism), attachment biology, and infant physiological regulation. Together, these data aid in the interpretation of findings in mouse models of the OXT system and generate new testable hypotheses for developmental roles for OXT in mammalian systems. Further, we describe OXTR ligand binding in select tissues of the near-term whole embryo at E18.5. Using male and female C57BL/6J mice at postnatal days (P) 0, 7, 14, 21, 35, and 60 we quantified OXTR ligand binding in several brain areas which changed across development. ![]() ![]() Here we report new data revealing dynamic ligand-binding distribution of OXTR in the developing mouse brain. ![]() Mouse models of OXT system genes have been particularly informative for the role of the OXT system in social behavior, however, the developing brain areas that could respond to ligand activation of the OXT receptor (OXTR) have yet to be identified in this species. It has been suggested that OXT plays an important role in the infant brain during caregiver attachment in nurturing familial contexts, but there is incomplete experimental evidence. Oxytocin (OXT) has drawn increasing attention as a developmentally relevant neuropeptide given its role in the brain regulation of social behavior. 2Department of Pediatrics, Children's Hospital Los Angeles and Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.1Vanderbilt Kennedy Center and Department of Pediatrics, Vanderbilt University School of Medicine, Vanderbilt University, Nashville TN, USA.
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