Defining a sensitive period for socialization in rodents

定义啮齿动物社会化的敏感期

• 批准号: 8538504
• 负责人: ARIE KAFFMAN
• 金额: $ 19.98万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8538504
• 关键词: Adolescence; Adolescent; Adult; Age; Animals; Behavior; Behavioral; Brain; Brain region; Cells; Ciliary Neurotrophic Factor; Complex; Data; Development; Developmental Process; Female; Fibroblast Growth Factor 2; Figs - dietary; Financial compensation; Goals; Hippocampus (Brain); Human; Hypothalamic structure; Intervention; Lead; Mammals; Mental Depression; Modeling; Molecular; Motivation; Mus; Neurons; Oxytocin; Play; Process; Psychopathology; Rodent; Role; Schizophrenia; Social Behavior; Social Development; Socialization; System; Testing; Work; adult neurogenesis; critical period; design; effective intervention; insight; mossy fiber; mouse model; nerve stem cell; neurogenesis; neurotrophic factor; novel strategies; paraventricular nucleus; postnatal; prevent; programs; response; social; young adult

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. .

描述（由申请人提供）：哺乳动物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，青少年时期的神经发生水平明显高于成年时期。重要的是，在幼年期（PND 30-60）阻断神经发生，但在成年期（PND 90-120）则不会导致雌性小鼠严重的社交缺陷。这些动物的特点是缺乏积极探索其他雌性的正常倾向，并且当不熟悉的雌性接近这些动物时，会反复尝试逃避社会接触（即逃避行为）。在这里，我们提出，青少年神经发生通过编程两个大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）中的幼年神经发生对于增加催产素（OT）细胞的数量是必要的，而催产素细胞又是启动与其他成年女性的社会接触所必需的。海马体 (HP) 中的幼年神经发生对于苔藓纤维的成熟至关重要，这是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敏感期，其中 OT 系统、苔藓纤维和社会行为的发展需要 NSC 的增殖。目标 2 中提出的工作将测试在青少年期 (PND 40-54) 和成年期 (PND 70-84) 施用神经营养因子 CNTF 和 FGF-2 是否可以逆转部分阻断青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，并将利用这种发展模型来设计新的策略来增强成年期的友善行为。 。