内侧视前核Esr1+神经元分类以及本能社会行为的神经调控

Innate social behaviors are essential for reproduction and for propagation of the species. Previous studies from our lab show that Esr1+ neurons in the medial preoptic area of the hypothalamus (mPOA) play an important role in the control of male-typical mating and female-typical pup care (Wei et al., Nature Communications). Based on these findings, in this grant we propose to further divide mPOA Esr1+ neurons into different sub-groups based on the criteria of expression of specific genetic markers, input/output connections, and single cell transcriptome. In addition, we propose to functionally study each subgroup in the context of male-typical mating and female-typical pup care. In doing so, we wish to answer the following questions: whether there are specific subgroups of Esr1+ neurons that are dedicated to regulate male-typical mating versus female-typical pup care, and secondly what are the neural mechanisms that govern sexually dimorphic display of behaviors. Probing the function of different neuronal subtypes is one of the major topics in neuroscience research currently. This proposal builds on our long-time research in the field of hypothalamic control of innate behaviors in the past and is well-founded. In dissecting the specific of role of different mPOA Esr1+ subpopulations in the control of male-typical mounting and female-typical pup care, we will generate empirical evidence that will eventually lead to the elucidation of basic principles that underlying neural control of complex social interactions.

本能社会行为对于物种繁衍至关重要。本实验室近期研究发现下丘脑内侧视前核Esr1+神经元在小鼠雄性求偶行为和母性行为中起关键作用 (Wei et al., Nature Communications)。在此基础上，本项目拟从分子标记、上下游联结和单细胞转录组这几个角度，对内侧视前核Esr1+神经元进一步分类，并且进行相应的功能学研究，以期找到特异性支配雄性求偶行为或者母性行为的Esr1+神经元集群，并进一步在此基础上探讨造成雌雄行为差异的神经机制。神经元分类是当下神经科学研究的热点之一，本项目建立在实验室长期以来对于下丘脑和本能社会行为研究的积累之上，具备理想的工作基础和工作条件，将系统阐述内侧视前核不同亚群的Esr1+神经元在雄性求偶行为和母性行为中所起到的具体作用，为解析大脑编码支配复杂社会行为的基本原则提供实验依据，具有重要的科学意义。

本项目拟从分子标记、上下游联结和单细胞转录组这几个角度，对内侧视前核Esr1+神经元进一步分类，并且进行相应的功能学研究，以期找到特异性支配雄性求偶行为或者母性行为的Esr1+神经元集群，并进一步在此基础上探讨造成雌雄行为差异的神经机制。在项目实施过程中，我们1）通过fMost 构建了内侧视前核Esr1+的全脑长程投射图谱，并对之进行了分类，找到对VTA和PAG 有侧枝投射的神经元为控制雄性求偶行为的关键神经元。2）分析了发育关键期中的内侧视前核的单细胞转录组。3)比较了雌雄视前区神经元的电生理参数差异。