--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 began analyzing 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. --This year, we completed a number of studies that confirmed the belief that the Avpr1b is important in regulating stress responses. In our Avpr1b KO mice, plasma adrenocorticotropin hormone and corticosterone levels induced by hypoglycemia are significantly decreased compared with wild-type littermates. In a model of chronic stress, plasma adrenocorticotropin hormone is decreased when compared with wild-type mice. Our results also suggest that Avpr1b plays a significant role in the hypothalamo-pituitary-adrenal axis response to acute immune stress. Dysregulation of the stress response is associated with the pathophysiology of depression, treatment of which with antidepressants involves increasing the availability of monamines at the synaptic cleft. We found that the Avpr1b is required to drive the HPA axis response to acute antidepressant treatment. --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 is allowing us to assess maternal behaviors of the forebrain KO dams as well as the subsequent behaviors of their offspring. We are seeing that this partial reduction in Oxtr leads to subtle deficits in maternal behavior, leading them to be poorer mothers and to be more susceptible to stress. It will be interesting to learn if poor mothering skills in humans are related to deficiencies in Oxt signaling. --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. --This fiscal year, using our knockout mice, we showed that a deficit in Avpr1b leads to reduced social investigation as well as deficits in hippocampally mediated temporal associations. These results suggest an important new role for Avp and the CA2 region pyramidal neurons, which express the Avpr1b, in associating past experiences with subsequent behaviors. --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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