Regulation Of Gene Expression In The Brain

National Institute Of Mental Health

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Abstract

Vasopressin (Avp) and oxytocin (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 have made gene knockouts (KO) for the mouse Oxt, and Avp 1a and Avp 1b receptors (Oxt, Avpr1a and Avpr1b, respectively) to investigate their specific roles in mediating behavior.[unreadable] Over the past year, we have continued to pursue the role of Avp and Oxt in mouse behavior. Specifically, we have shown that the decrease in aggression found in the Avpr1b KO is limited to the its social component, including maternal, but not predatory. Furthermore, the offensive retaliatory component of defensive behavior is lacking, but not the protective aspects. In contrast, we observed relatively minor deficits in the Avpr1a KOs. These mice have a slightly longer circadian tau (length of the day in constant darkness). They also have significant deficits in olfaction but, surprisingly, not in aggression, social recognition, or anxiety- and depression-related behaviors. Finally, we have recently created and started studying a conditional KO of the Oxtr. This line has the coding region flanked by LoxP sites to allow us to temporally and spatially regulate the expression of the Oxtr. We have initially generated total and postnatal day 28 forebrain knockouts. Unlike Oxt and total Oxtr KOs, the forebrain 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 have also been working on the creation of a KO for the micro RNA, miR-7b, to study its role in regulating C-Fos expression and, consequently, expression of Avp.