Dissecting the neural circuits of maternal behaviors

简要说明 在哺乳动物物种中，母性行为是一种先天的社会行为， 后代的生存和成功。几十年的研究已经确定了一种进化上的 保守的下丘脑区，内侧视前区（MPOA），是必不可少的， 母性行为的表现。然而，鉴于MPOA包含异构和 虽然多功能细胞的存在，但与母性行为相关的细胞的身份仍然不清楚。 最近，使用一系列最先进的功能操作和体内记录工具，我们 发现MPOA中表达雌激素受体α（Esr 1）的细胞是必需的， 在母性行为中充分和自然地活跃。我们建议的研究将扩展到 这些重要的发现，通过寻求进一步研究神经回路延伸，从 人口在目标1中，我们将结合联合收割机逆行追踪和顺行追踪以及体外切片 电生理学来鉴定雌性小鼠中MPOA Esr 1+细胞的下游靶标。在 目的2，我们将采用光遗传学和药物遗传学工具来解决的功能作用， 每个MPOA通路及其相关的下游细胞在驱动各种成分， 母性行为在目标3中，我们将使用体内光学和电生理记录， 检查MPOA下游区域细胞的自然反应， 行为，以及信息从MPOA转移到其 下游细胞这个项目解决了神经科学中的一个基本问题， 母性行为的产生与理解和治疗有缺陷的 母亲回路导致异常的母亲行为，如忽视和虐待儿童。

SUMMARY STATEMENT Across mammalian species, maternal behavior is an innate social behavior essential for the survival and success of the offspring. Decades of research has identified an evolutionarily conserved hypothalamic area, the medial preoptic area (MPOA), as being essential for the expression of maternal behavior. However, given that the MPOA contains heterogeneous and multifunctional cells, the identity of cells relevant for maternal behavior remains unclear. Recently, using a series of state-of-art functional manipulation and in vivo recording tools, we found that cells in the MPOA that express the estrogen receptor alpha (Esr1) are necessary, sufficient and naturally active during maternal behaviors. Our proposed study will expand on these essential findings by seeking to further investigate the neural circuits extended from the population. In Aim 1, we will combine retrograde and antegrade tracing and in vitro slice electrophysiology to identify the downstream targets of the MPOA Esr1+ cells in female mice. In Aim 2, we will employ optogenetic and pharmacogenetic tools to address the functional role of each MPOA pathway and its related downstream cells in driving various components of maternal behaviors. In Aim 3, we will use in vivo optical and electrophysiological recordings to examine the natural responses of cells in the MPOA downstream regions during maternal behaviors, and the principles that underlie the transfer of information from the MPOA to its downstream cells. This project addresses a basic question in neuroscience regarding how maternal behavior is generated and is relevant for understanding and treating a defective maternal circuit that causes abnormal maternal behaviors, such as child neglect and abuse.