Dissecting the neural circuits of maternal behaviors

摘要报表 在哺乳动物物种中，母性行为是一种天生的社会行为，对 后代的生存和成功。几十年的研究已经在进化上发现了一种 保守的下丘脑区，即内侧视前区(MPOA)，对于 母性行为的表现。然而，鉴于MPOA包含异质的和 多功能细胞，与母体行为相关的细胞的身份尚不清楚。 最近，使用了一系列最先进的功能操作和活体记录工具，我们 发现MPOA中表达雌激素受体α(ESR1)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 这些重要的发现是通过进一步研究神经回路从 人口。在目标1中，我们将逆行和顺行示踪与体外切片相结合 电生理学以确定雌性小鼠MPOA ESR1+细胞的下游靶点。在……里面 目标2，我们将使用光遗传学和药物遗传学工具来解决 每条MPOA途径及其相关的下游细胞都在驱动不同的成分 母性行为。在目标3中，我们将使用活体光学和电生理记录来 检测母亲孕期MPOA下游区域细胞的自然反应 行为，以及从MPOA向ITS传递信息所依据的原则 下游细胞。这个项目解决了神经科学中的一个基本问题，即如何 母性行为是产生的，并与理解和治疗缺陷相关 导致异常母体行为的母体回路，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.