Integrating social and state cues that motivate vocal behavior

整合激发声音行为的社会和国家线索

基本信息

批准号：
10428349
负责人：
Joel Tripp
金额：
$ 6.98万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10428349
关键词：
Address Advertisements Affect Aggressive behavior Androgens Animals Behavior Behavioral Brain Brain region Cell Nucleus Cells Complex Cues Data Dimensions Educational process of instructing Environment Exposure to Faculty Feeding behaviors Fellowship Female Foundations Frequencies Future Genes Genetic Transcription Genomics Glucocorticoids Hormonal Hormones Hypothalamic structure Immunoprecipitation Individual Injections Label Laboratories Laryngeal muscle structure Leptin Literature Mental Health Mental disorders Mentorship Messenger RNA Methods Motivation Mus Neurodevelopmental Disorder Neurons Neurosciences Partner in relationship Personal Satisfaction Population Positioning Attribute Process Proteins RNA Regulation Research Rodent Rodent Model Role Saline Shapes Signaling Molecule Social Behavior Social Controls Social Environment Social Interaction Stress System Testing Texas Tissues Training Transcript Universities Vertebrates Viral Wakefulness Well in self Work activity marker adipokines austin brain cell candidate marker career cell type cricothyroid muscle energy balance experience experimental study hormonal signals insight mad itch virus male neural circuit neural model neuromechanism novel paraventricular nucleus physical conditioning programs rabies viral tracing receptor relating to nervous system reproductive response responsible research conduct social social cognition social communication social deficits social engagement social influence tenure track transcriptome sequencing vocal control vocalization

项目摘要

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.

项目概要积极的社交互动对于许多人的心理健康和身体健康至关重要。神经发育障碍影响社交参与动机或受其影响。受多种因素的影响，包括外部环境，特别是社会背景，以及内部环境压力、生育状况和精力状态等因素通常会影响社交。动机是孤立研究的；然而，我们知道在实验室之外这些因素是相互作用的该提案利用了一种新颖的系统，即阿尔斯通的歌唱鼠标（Scotinonomys）。 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：感知的能量平衡是研究这些问题的理想物种，因为对社交环境的操纵（例如接触潜在的伴侣或播放同种歌曲）以及荷尔蒙状态（例如雄激素、糖皮质激素和瘦素）都会影响声音的参与。通过三个目标，我将检验以下假设：社会背景和能量平衡的线索是整合到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。匹兹堡大学的斯特里克利用狂犬病病毒追踪喉部肌肉的输入来识别大脑这一目标将证实能量传感核心位于老鼠发声的上游。歌唱小鼠发声回路中的室旁下丘脑或者让我完善我的假设如果有必要，选择一个新的目标核接下来，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旨在识别整合社会背景和感知能量状态的神经元。我将使用神经激活标记物磷酸-S6 来检验室旁下丘脑的假设神经元会因接触女性、注射瘦素或两者而增加活动。 PhosphoTRAP，一种对最近活跃的神经元的 RNA 进行测序的方法，以识别由室旁下丘脑的神经元由女性暴露、瘦素注射或两者同时激活。最后，在目标 3 中，我将使用室旁下丘脑的单核 RNA 测序来识别细胞类型，并将这些与目标 2 中找到的候选标记相关联。这将使我能够确定是否富含活性细胞的转录物对应于特定的细胞类型，这些目标将共同确定一个回路。以及其中的特定细胞类型，它们整合了影响发声努力的社会和内部线索，增强了我们的能力了解驱动社会动机的复杂过程并为未来的研究奠定基础通过这个奖学金，我将不会获得关于社会动机和哺乳动物发声的研究。不仅是上述的技术培训，而且还包括负责任的研究行为的进一步培训，教学和指导对于我未来的终身教授职位来说是非常宝贵的。