Integrating social and state cues that motivate vocal behavior

项目摘要 积极的社会互动对心理健康和身体健康至关重要。许多心理和 神经发育障碍影响社会参与的动机或受其影响。这种动机是 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、生殖状况和精力状态等因素。通常，这些因素对社会的影响 动机是孤立地研究的;然而，我们知道，在实验室之外，这些因素相互作用， 是相互结合的。这项建议利用了一种新的系统，阿尔斯顿的歌唱鼠（Scotinomys teguina），研究整合社会背景和内部状态的一个重要维度的神经回路： 感知能量平衡。唱歌的老鼠是研究这些问题的理想物种， 对社会环境的操纵（例如暴露于潜在的配偶或播放同种歌曲），以及 激素状态（例如雄激素、糖皮质激素和瘦素）都可以影响发声参与。 通过三个目标，我将测试假设，即社会背景和能量平衡的线索是 整合在室旁下丘脑的特定细胞类型中。在目标1中，我将在Peter的实验室工作 利用狂犬病病毒追踪喉肌的输入来识别大脑 电路潜在的唱歌鼠标发声。这一目标将证实，能量感应核位于 室旁下丘脑在唱歌的老鼠发声回路或允许我完善我的假设， 必要时选择新的靶核。接下来，我将在我的赞助商史蒂芬·菲尔普斯的实验室工作， 德克萨斯大学奥斯汀分校，以确定整合社会背景和感知能量状态的神经元。在目标2 我将使用神经激活标记磷酸S6来检验室旁下丘脑 神经元响应于暴露于雌性、瘦素注射或两者而增加活性。然后，我将使用 PhosphoTRAP是一种对最近活跃的神经元的RNA进行测序的方法，用于鉴定由 室旁下丘脑的神经元被雌性暴露、瘦素注射或两者激活。 最后，在目的3中，我将使用室旁核下丘脑的单核RNA测序来鉴定细胞， 在该地区的类型，并将这些目标2中发现的候选标记。这样我就能确定 在活性细胞中富集的转录物对应于特定的细胞类型。总之，这些目标将确定一个电路 以及其中的特定细胞类型，这些细胞整合了影响发声努力的社会和内部线索， 了解驱动社会动机的复杂过程，并为未来的研究奠定基础 社会动机和哺乳动物发声的研究。通过这份友谊，我不会得到 除了上述技术培训外，还包括负责开展研究方面的进一步培训， 教学，和指导，这将是我未来的职业生涯在终身教职的位置无价。

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.