Microcircuits underlying murine parental behavior

 描述(申请人提供)：许多具有相当大疾病负担的严重精神障碍，如自闭症谱系障碍、精神分裂症和严重抑郁障碍，都以严重的社会障碍为特征。目前，人们对这些社会缺陷的根源知之甚少，缺乏有效的诊断和治疗选择。先进的分子和基因技术使发现涉及社会行为的特定神经回路成为可能，促进了针对社会缺陷疾病的诊断和新的治疗方法的发展。我们建议利用新开发的分子和遗传工具来发现和表征参与父母照料的特定神经群体和回路，这是一种对 子孙后代的生存和福祉。雄性和雌性小鼠对婴儿表现出从属或激进化的行为，这取决于先前的社会经验。在最近发表的工作中，我们发现了一个特定的下丘脑神经元亚群，它们对控制男性和女性的育儿行为是必不可少的。这一发现为我们提供了一个独特的切入点，从基因上剖析父母照料的行为回路及其内在调节 以及环境因素。使用遗传和功能工具的组合，我们的目标是表征参与父母行为的回路(目标I)，并揭示驱动对幼崽的激励性行为的神经元亚群(目标II)。我们将使用尖端分子技术，通过追踪基因定义的神经元种群的输入和输出并操纵它们的活动，来确定这些遗传定义的神经种群和相关的投影在育儿或针对幼崽的激励性行为中的功能作用。在AIM III中，我们 将进行无偏见的基因表达分析，以发现影响与男性附属或激动性行为相关的神经元和回路的不同活动的因素 雌性，在不同的生理环境中。

 DESCRIPTION (provided by applicant): Many severe mental disorders with considerable disease burden such Autism Spectrum Disorders, Schizophrenia, and Major Depressive Disorder are characterized by profound social impairments. At present, there is little understanding of the origin of these social deficits, and efficient diagnosis and therapeutic options are lacking. Advanced molecular and genetic techniques make the discovery of specific neural circuits involved in social behavior possible, facilitating the development of diagnostics and novel therapeutic approaches specific to disorders with social deficits. We propose to take advantage of newly developed molecular and genetic tools to uncover and characterize the specific neural populations and circuits involved in parental care, a social behavior essential for the survival and well-being of the offspring. Male and female mice show either affiliative or agonistic behavior toward infants depending on prior social experience. In recently published work, we uncovered a specific subpopulation of hypothalamic neurons that are essential for the control of male and female parenting behavior. This finding provides us with a unique entry point to genetically dissect behavior circuits underlying parental care and their modulation by intrinsic and environmental factors. Using a combination of genetic and functional tools, we aim to characterize the circuit involved in parental behavior (Aim I) and uncover neuronal subpopulations driving agonistic behavior toward pups (Aim II). We will determine the functional role of these genetically defined neural populations and associated projections in parenting or agonistic behavior toward pups using cutting-edge molecular techniques by tracing inputs and outputs to genetically defined neuronal populations and manipulating their activity. In Aim III, we will perform an unbiased gene expression analysis to discover factors influencing the differential activity of the neurons and circuits associated with affiliative or agonistic behavior in males and females, and in different physiological circumstances.