Dissecting the neural circuits of maternal behaviors

剖析母亲行为的神经回路

• 批准号: 9917791
• 负责人: Dayu Lin
• 金额: $ 49.38万
• 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/9917791
• 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.

概要声明 在哺乳动物物种中，母性行为是一种与生俱来的社会行为，对于 后代的生存和成功。数十年的研究已经确定了一种进化的 下丘脑的保守区域，即内侧视前区（MPOA），对于 母亲行为的表达。然而，鉴于 MPOA 包含异构和 多功能细胞，与母体行为相关的细胞的身份仍不清楚。 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 (Esr1) 的细胞是必需的， 在母亲行为过程中充分且自然活跃。我们提出的研究将扩展 通过寻求进一步研究从神经回路延伸出来的这些重要发现 人口。在目标1中，我们将结合逆行和顺行追踪以及体外切片 电生理学来识别雌性小鼠 MPOA Esr1+ 细胞的下游靶标。在 目标 2，我们将利用光遗传学和药物遗传学工具来解决 每个 MPOA 通路及其相关下游细胞驱动各种组件 母亲的行为。在目标 3 中，我们将使用体内光学和电生理记录来 检查母体期间 MPOA 下游区域细胞的自然反应 行为以及信息从 MPOA 传输到其自身的原则 下游细胞。该项目解决了神经科学中的一个基本问题，即如何 母性行为的产生与理解和治疗缺陷相关 导致母亲异常行为的母亲回路，例如忽视和虐待儿童。