Defining a sensitive period for socialization in rodents

描述（由申请人提供）：哺乳动物的幼年期的特点是参与社会行为的动机和能力急剧增加。然而，支持这一发育过程所需的细胞和分子机制尚未阐明。我们最近发现，与成年期相比，青少年期的神经发生水平明显更高。重要的是，在幼年期（PND 30-60）而不是成年期（PND 90-120）阻断神经发生会导致雌性小鼠严重的社会缺陷。它们的特征是缺乏积极探索其他雌性的正常倾向，当不熟悉的雌性接近它们时，它们会反复尝试逃避社会接触（即逃跑行为）。在这里，我们提出青少年神经发生通过编程两个脑回路的成熟来定义友好行为的关键时期。下丘脑室旁核（PVN）的幼年神经发生是增加催产素（OT）细胞数量所必需的，而催产素（OT）细胞又对启动与其他成年雌性的社会接触是必要的。海马幼年神经发生（HP）对苔藓纤维的成熟至关重要，这是一个防止逃避行为所需的发育过程。目标1中提出的工作将定义OT系统、苔藓纤维和社会行为的发展需要NSC扩散的敏感时期。目标2中提出的工作将测试在少年期（PND 40-54）和成年期（PND 70-84）给予神经营养因子CNTF和FGF-2是否可以逆转部分阻断少年神经发生后出现的发育和社会缺陷。这些研究将确定幼年神经发生是否定义了雌性小鼠社会发展的关键时期，并将利用这一发育模型设计新的策略来增强成年后的友好行为。

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. .