Dissecting the neural circuits of maternal behaviors

剖析母亲行为的神经回路

• 批准号: 10401252
• 负责人: Dayu Lin
• 金额: $ 48.4万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-10 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10401252
• 关键词: Address; Aggressive behavior; Alpha Cell; Animal Model; Area; Automobile Driving; Behavior; Cells; Characteristics; Child Abuse and Neglect; Child Development; Data; Electrophysiology (science); Estrogen Receptor alpha; Female; Fiber; Goals; Grooming; Health; Human; Hypothalamic structure; In Vitro; Infant; Investigation; Label; Mammals; Maternal Behavior; Medial; Mediating; Methods; Mothers; Mus; Neurons; Neurosciences; Optics; Output; Pathway interactions; Pattern; Pharmacogenetics; Photometry; Population; Preoptic Areas; Research; Retrieval; Role; Series; Slice; Social Behavior; Synapses; Tracer; Ventral Tegmental Area; Viral; Work; behavioral impairment; cell type; experience; extracellular; improved; in vivo; loss of function; maternal caregiving; neural circuit; neurobehavioral; offspring; optogenetics; public health relevance; pup; relating to nervous system; reproductive; response; success; tool

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.

摘要声明 在整个哺乳动物的物种中，母性行为是一种天生的社会行为，对 后代的生存和成功。数十年的研究已在进化上确定 保守的下丘脑区域，内侧前区域（MPOA），对于 孕产妇行为的表达。但是，鉴于MPOA包含异质和 多功能细胞，与母体行为相关的细胞的身份尚不清楚。 最近，使用一系列最先进的功能操纵和体内记录工具，我们 发现表达雌激素受体α（ESR1）的MPOA中的细胞是必要的， 在孕产妇行为期间足够且自然活跃。我们提出的研究将扩大 这些基本发现是通过寻求进一步研究从 人口。在AIM 1中，我们将结合逆行和前进痕迹和体外切片 电生理学以鉴定雌性小鼠MPOA ESR1+细胞的下游靶标。在 AIM 2，我们将采用光遗传学和药物遗传学工具来解决 每个MPOA途径及其相关的下游细胞驱动各种组件 孕产妇行为。在AIM 3中，我们将使用体内光学和电生理记录到 检查母体中MPOA下游区域中细胞的自然反应 行为以及信息从MPOA转移到其的原则 下游细胞。该项目解决了神经科学中的一个基本问题 产生孕产妇的行为，与理解和治疗有缺陷有关 产生异常行为的产妇循环，例如儿童忽视和虐待。