--We have continued this fiscal year to study our gene knockouts (KO) of the mouse oxytocin (Oxt) and vasopressin (Avp) 1a and 1b receptors (Oxtr, Avpr1a and Avpr1b, respectively) to investigate their specific roles in mediating behavior. We are also continuing to analyze whether we were successful in creating a conditional KO of the Avpr1b gene which would allow more precise spatial and temporal regulation of its expression. Avp and Oxt are neurohormones that are best known for their peripheral actions in regulating salt and water balance, blood pressure, lactation and parturition. However, numerous pharmacological studies have implicated these hormones in various behaviors as well, including aggressive, affiliative, and maternal. --We recently started studying a conditional KO of the Oxt receptor (Oxtr). This line has the coding region flanked by special DNA sequences to allow us to temporally and spatially regulate the expression of the Oxtr. Unlike Oxt and total Oxtr KOs, mice with relatively forebrain-specific inactivation of the Oxtr KOs are able to lactate and their pups survive. This allows us to assess maternal behaviors of the forebrain KO dams as well as the subsequent behaviors of their offspring. We found that both Oxtr/ and OxtrFB/FB females appear to have largely normal maternal behaviors. However, with first litters, approximately 40% of the OxtrFB/FB knockout dams experienced high pup mortality, compared to fewer than 10% of the Oxtr+/+ dams. We then went on to test whether or not this phenotype occurred in subsequent litters or when the dams were exposed to an environmental disturbance. We found that regardless of the degree of external disturbance, OxtrFB/FB females lost more pups on their first and second litters compared to wildtype females. It will be interesting to learn if poor mothering skills in humans are related to deficiencies in Oxt signaling. --This year, we completed a number of studies that confirmed the belief that the Avpr1b is important in regulating aggressive responses. In our Avpr1b KO mice, we found that upon breeding the mutation onto a naturally more feral and aggressive background, those mice became less aggressive. We also showed that while Avpr1b -/- mice may be able to form dominance hierarchies, they appear to employ alternate strategies. --This fiscal year, we showed that deficits in Oxtr and Oxt lead to deficits in social recognition, with especial importance for intra-strain recognition. These results help refine the potential role of the Oxt system in social memory. We are continuing to investigate social memory in our Oxtr, Avpr1a and Avpr1b knockouts with our new paradigm. --We are just expanding our exploration of a small, non-coding RNA, miR-7b, that we discovered regulates levels of an important gene regulator, c-Fos. We believe that we have just created a conditional KO of this gene and hope to further our understanding of miR-7bs role in brain function in the coming year.
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