Integrating social and state cues that motivate vocal behavior

项目总结 积极的社会互动对心理健康和身体健康至关重要。许多精神和精神上的 神经发育障碍影响或受到社交动机的影响。这一动机是 受各种因素的影响，包括外部环境，特别是社会背景以及内部 压力、生殖状态和精力状态等因素。通常，这些因素对社会的影响 动机是孤立研究的；然而，我们知道，在实验室之外，这些因素相互作用并 是相互融合的。这一建议利用了一种新的系统，阿尔斯顿的鸣鼠(Scotinomys Teguina)，研究整合了社会背景和内部状态的一个重要维度的神经回路： 感知到的能量平衡。会唱歌的老鼠是研究这些问题的理想物种，比如 对社会环境的操纵(例如，接触潜在伴侣或播放同种歌曲)和 荷尔蒙状态(如雄激素、糖皮质激素和瘦素)都会影响发声。 通过三个目标，我将检验这样一个假设，即社会背景和能量平衡的线索是 整合在下丘脑室旁的特定细胞类型中。在目标1中，我将在彼得的实验室工作 Strick在匹兹堡大学使用狂犬病病毒追踪喉部肌肉的输入来识别大脑 歌唱鼠标发声的基础电路。这一目标将证实，能量感应核位于 下丘脑室旁核在鸣叫的老鼠的声道中，还是让我来完善我的假设和 如有必要，选择一个新的靶核。接下来，我将在我的赞助商史蒂文·菲尔普斯的实验室工作， 德克萨斯大学奥斯汀分校识别整合了社会背景和感知到的能量状态的神经元。在AIM 2 我将使用神经激活标记物磷酸化S6来验证下丘脑室旁核 神经元在暴露于雌性、注射瘦素或两者兼而有之的情况下会增加活动。然后，我将使用 一种从最近活跃的神经元中对RNA进行测序的方法，以识别由 下丘脑室旁神经元被女性暴露或注射瘦素激活，或两者兼而有之。 最后，在目标3中，我将使用下丘脑室旁核的单核rna测序来鉴定细胞 类型，并将这些类型与在Aim 2中找到的候选标记相关联。这将使我能够确定 活跃细胞中丰富的转录本对应于特定的细胞类型。加在一起，这些目标将确定一条赛道 以及其中特定的细胞类型，整合了影响发声努力的社会和内部线索，增强了我们的 理解驱动社会动机的复杂过程，并为未来的研究奠定基础 使用这种新物种的社会动机和哺乳动物发声。通过这一团契，我不会得到 不仅是上述的技术培训，而且还有负责任的研究行为方面的进一步培训， 教学和指导对我未来在终身教职岗位上的职业生涯将是无价的。

PROJECT SUMMARY Positive social interactions are critical for mental wellness and physical health. Many mental and neurodevelopmental disorders affect or are affected by the motivation to socially engage. This motivation is influenced by a myriad of factors that include external environment, particularly social context, as well as internal factors such as stress, reproductive status, and energetic state. Typically, the influence of these factors on social motivation are studied in isolation; however, we know that outside of the laboratory these factors interact and are integrated with one another. This proposal makes use of a novel system, Alston’s singing mouse (Scotinomys teguina), to investigate the neural circuit integrating social context and one important dimension of internal state: perceived energy balance. Singing mice are an ideal species in which to investigate these questions, as manipulations to social environment (e.g. exposure to potential mates or playback of conspecific song) and hormonal state (e.g. androgens, glucocorticoids, and leptin) can all influence vocal engagement. Through three aims, I will test the hypothesis that cues of social context and energy balance are integrated in specific cell types in the paraventricular hypothalamus. In Aim 1, I will work in the lab of Peter Strick at the University of Pittsburgh, using rabies virus tracing of inputs to laryngeal muscle to identify the brain circuit underlying singing mouse vocalization. This aim will confirm that energetic-sensing nuclei sit upstream of the paraventricular hypothalamus in the singing mouse vocal circuit or allow me to refine my hypothesis and choose a new target nucleus if necessary. Next, I will work in the lab of my sponsor Steven Phelps, at the University of Texas-Austin to identify neurons integrating social context and perceived energetic state. In Aim 2 I will use the neural activation marker, phospho-S6, to test the hypothesis that paraventricular hypothalamus neurons increase activity in response to exposure to females, leptin injections, or both. Then, I will use PhosphoTRAP, a method of sequencing RNA from recently active neurons, to identify transcripts expressed by neurons of the paraventricular hypothalamus that are activated by female exposure, leptin injection, or both. Finally, in Aim 3, I will use single-nucleus RNA-sequencing of the paraventricular hypothalamus to identify cell types in the region and relate these to candidate markers found in Aim 2. This will allow me to determine whether transcripts enriched in active cells correspond to specific cell types. Together, these aims will identify a circuit and specific cell types within it that integrate social and internal cues that influence vocal effort, enhancing our understanding of the complex processes that drive social motivation and laying the groundwork for future studies of social motivation and mammalian vocalization using this novel species. Through this fellowship I will gain not only the technical training described above, but also further training in the responsible conduct of research, teaching, and mentorship that will be invaluable for my future career in a tenure-track faculty position.