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Parental care and sensory stimulation are critical environmental factors that influence oxytocin (OXT) and its receptor (OXTR). Because developmental Oxt mRNA expression is enhanced by sensory-rich early life experience and reduced by sensory deprivation, we predicted that compared to wild-type (WT) littermates, mice with congenital loss of OXTR (OXTR KO), as a genetically induced deprivation, would show impaired Oxt mRNA expression in the offspring hypothalamus during development. Oxt mRNA levels of male and female OXTR KO mice were not different from WT littermates from postnatal day (P)0 to P6, although, by P8, OXTR KO showed significantly decreased Oxt mRNA expression in the hypothalamus compared to WT littermates. At P14, male and female OXTR KO mice had significantly decreased Oxt mRNA expression specifically in the paraventricular nucleus (PVN), but not the supraoptic nucleus (SON), compared to WT littermates. We investigated whether this effect persisted in adulthood (P90) and found a significant genotype by sex interaction where male OXTR KO mice displayed a reduction in Oxt expression specific to the PVN compared to male WT littermates. By contrast, male and female OXTR KO adults had increased Oxt mRNA levels in the SON. These findings suggest that OXTR plays a role in developmental Oxt mRNA expression with sex by genotype interactions apparent at adulthood. We then measured OXT and neural activation in the PVN and SON at P14. We observed more OXT-immunoreactive cells in the PVN of OXTR KO mice but significantly fewer c-Fos immunoreactive cells. There were no genotype differences in immunoreactivity for OXT and no c-Fos activity in the SON at P14. Combined, these data suggest that OXTR WT P14 mice have more PVN activity and are more likely to release OXT than OXTR KO mice. Future experiments are warranted to understand which OXTR-expressing neural circuits modulate the development of the PVN oxytocin system.

Arginine vasopressin modulates pairbond formation in the monogamous prairie vole (Microtus ochrogaster). Our laboratory has investigated the genetic and neural mechanisms by which vasopressin and its V1a receptor (V1aR) regulate social attachment between mates. Non-monogamous vole species show strikingly different distribution patterns of brain V1aR expression compared to monogamous species, and these patterns are thought to arise from species differences in the respective promoter sequences of the V1aR gene. Individual differences in prairie vole V1aR patterns may also reflect individual differences in promoter sequences. Pharmacological and genetic manipulation of the specific brain regions that express V1aR in the 'monogamous pattern' allows multilevel examination of the neural circuits that underlie pairbond formation in monogamous species. For example, V1aR are expressed in brain regions involved in reward circuitry in monogamous vole species and have been implicated in pairbonding. V1aR are also highly expressed in regions implicated in the olfactory processing of sociosexual behaviour. We hypothesize that both circuits of reward and olfactory memory underlie the cognitive mechanisms that control pairbonding. When used in conjuction, genetic and cellular analyses of a complex social behaviour can provide a coherent framework with which to examine the role of the vasopressin system in species evolution and neural control of behaviour.