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：
10668359
负责人：
Joel Tripp
金额：
$ 7.38万
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/10668359
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 Genetic Transcription Genomics Glucocorticoids Hormonal Hormones Hypothalamic structure Immunoprecipitation Individual Injections Label Laboratories Laryngeal muscle structure Leptin Literature Maps Mental Health Mental disorders Mental health promotion 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 neural circuit neural model neuromechanism novel paraventricular nucleus physical conditioning programs rabies viral tracing receptor reproductive response responsible research conduct single nucleus RNA-sequencing 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.

项目摘要积极的社会互动对于精神健康和身体健康至关重要。许多精神和神经发育障碍会影响或受社会参与动机的影响。这种动机是受到包括外部环境，尤其是社会环境以及内部的无数因素的影响压力，生殖状况和能量状态等因素。通常，这些因素对社会的影响动机是孤立的；但是，我们知道，在实验室之外，这些因素相互作用，并且彼此集成。该建议利用了一个新型系统，即阿尔斯顿的唱歌鼠标（Scotinomys Teguina），调查整合社会环境和内部状态的重要方面的神经循环：感知的能量平衡。唱歌小鼠是研究这些问题的理想物种，例如对社交环境的操纵（例如，接触潜在的伴侣或特定歌曲的播放）和激素状态（例如雄激素，糖皮质激素和瘦素）都会影响声音参与。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集成在旁脊髓下丘脑中的特定细胞类型中。在AIM 1中，我将在彼得的实验室工作在匹兹堡大学的史密斯（Strick 唱歌鼠标发声的基础电路。这个目标将确认能量感应核坐在唱歌的小鼠声乐中的室室下丘脑，或者让我完善我的假设和如有必要，选择一个新的目标核。接下来，我将在赞助商史蒂文·菲尔普斯（Steven Phelps）的实验室工作德克萨斯大学奥斯汀分校识别整合社会环境和感知能量状态的神经元。在目标2中我将使用Neuro激活标记磷酸-S6进行测试，以下假设：神经元因接触女性，瘦素注射或两者而增加活性。然后，我会使用 Phosphotrap是一种测序来自最近活跃神经元的RNA的方法，以识别由通过女性暴露，瘦素注射或两者激活的旁丘脑下丘脑的神经元。最后，在AIM 3中，我将使用单核下丘脑的单核RNA测序来鉴定细胞该地区的类型以及这些类型与AIM 2中的候选标记有关。这将使我能够确定是否是否富含活性细胞的转录物对应于特定的细胞类型。这些目标在一起将确定电路以及其中的特定细胞类型，这些类型整合了影响声音努力的社会和内部提示，增强了我们的了解驱动社会动机并为未来研究奠定基础的复杂过程使用这种新型物种的社会动机和哺乳动物发声。通过这个奖学金，我不会获得只有上述技术培训，但也进一步培训了负责任的研究，教学和心态对于我未来的职业生涯将是一个终身任职的职位，这将是无价的。