Defining a sensitive period for socialization in rodents

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DESCRIPTION (provided by applicant): The juvenile period in mammals is characterized by a dramatic increase in the motivation and the capacity to engage in social behavior. However, the cellular and molecular mechanisms necessary to support this developmental process have not been elucidated. We recently showed that levels of neurogenesis are significantly higher in the juvenile period compared to adulthood. Importantly, blocking neurogenesis during the juvenile period (PND 30-60), but not in adulthood (PND 90-120) causes profound social deficits in female mice. These are characterized by the absence of the normal tendency to actively explore other females and repeated attempts to evade social contact (i.e. escape behavior) when an unfamiliar female approached these animals. Here we propose that juvenile neurogenesis defines a critical period for amicable behavior by programming the maturation of 2 brain circuits. Juvenile neurogenesis in the paraventricular nucleus of the hypothalamus (PVN) is necessary to increase the number of oxytocin (OT) cells, which in turn is necessary to initiate social contact with other adult females. Juvenile neurogenesis in the hippocampus (HP) is critical for maturation of mossy fibers, a developmental process that is needed to prevent escape behavior. Work proposed in aim 1 will define the sensitive period in which the development of the OT system, mossy fibers, and social behavior, requires proliferation of NSC. Work proposed in aim 2 will test whether administering the neurotrophic factors CNTF and FGF-2 during the juvenile period (PND 40-54) and adulthood (PND 70-84) can reverse the developmental and social deficits seen after partially blocking juvenile neurogenesis. These studies will determine whether juvenile neurogenesis defines a critical period for social development in the female mouse, and will use this developmental model to design novel strategies to enhance amicable behavior in adulthood. . PUBLIC HEALTH RELEVANCE: New neurons continue to be generated and added into two brain regions in the prepubescent and mature adult mammalian brain. We found that ablating this process in peripubescent mice led to profound abnormalities in social behavior that were not evident when the same process was ablated in fully adult mice. A better understanding of the mechanism by which prepubescent neurogenesis programs complex behaviors in adult rodents, is likely to provide new insights into the contribution of this developmental process to human psychopathologies that first emerge during late adolescence such as schizophrenia and depression.