Dissecting sex hormone effects on genes, neurons, and behavior using cichlid fish

使用慈鲷剖析性激素对基因、神经元和行为的影响

• 批准号: 10275847
• 负责人: Scott Alan Juntti
• 金额: $ 37.83万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10275847
• 关键词: Adult; Affect; Aggressive behavior; Behavior; Biological Models; Brain; Cells; Cichlids; Clustered Regularly Interspaced Short Palindromic Repeats; Complex; Development; Endocrine system; Female; Foundations; Gene Expression; Gene Transfer Techniques; Genes; Genetic Transcription; Genome; Genomics; Goals; Gonadal Hormones; Gonadal Steroid Hormones; Hormones; Incidence; Ligands; Mediating; Mental disorders; Neural Pathways; Neurons; Neurophysiology - biologic function; Pattern; Population; Prevalence; Production; Progesterone Receptors; Progestins; Prostaglandins; Receptor Signaling; Reproductive Behavior; Research; Shapes; Signal Transduction; Smell Perception; Social Behavior; Social Controls; Stereotyping; Steroids; System; Technology; Time; Vertebrates; Woman; behavior change; experimental study; hormonal signals; hypothalamic pituitary gonadal axis; insight; male; men; neural circuit; neuropsychiatry; programs; receptor; sensory input; sex; steroid hormone receptor; transcription factor

Juntti | Project Summary The overarching goal of my research program is to understand how hormones shape the neural pathways that control social behavior. Gonadal hormones are key regulators of development and adult neural function, and their signaling leads to profound differences in vertebrate animal reproductive and aggressive behaviors across sexes. Differences in hormone signaling across men and women could contribute to discrepancies in incidence of neuropsychiatric conditions, but the neuronal and transcriptional basis for their actions are not clear. These hormones may determine the connectivity of cells, their activity patterns, or both. Reproductive behaviors in cichlid fish are an ideal model system to understand how hormones impact gene transcription and neural circuit function. Cichlid social behaviors have been studied for nearly a century, and are complex yet stereotyped and quantifiable. Dozens of cichlid species have sequenced genomes, and we have pioneered CRISPR gene editing and transgenesis in these species. We have identified a population of neurons sensitive to the hormones progestin and prostaglandin F2α (PGF) that is essential for spawning behavior. Progestin receptor (PR) signaling regulates gene expression in these cells, while PGF and its receptor, Ptgfr, are sufficient and necessary to initiate spawning. We seek to determine the contribution of Ptgfr+ cells to a variety of social behaviors through genetically directed manipulation of these cells. The implementation of the QF-QUAS system for the first time in cichlids will permit studies of these and other cells. Like other steroid hormone receptors, PR acts as a ligand-activated transcription factor. However, its genomic targets are not known in brain, and so it is not clear how it regulates behavior. We will identify how PR regulates cichlid behavior routines and determine the genomic targets of PR that underlie its actions. The production of progestin (and other steroids) is regulated by the hypothalamic-pituitary-gonadal axis. Sensory inputs regulate the production of progestin in cichlids: male odorants promote its synthesis. We will identify cell groups that mediate this signaling from olfaction to the endocrine system. These approaches will build upon our previous findings and leverage technologies that we have developed, together yielding insights into how the vertebrate brain regulates and responds to sex hormones. These experiments will lay a foundation for understanding the gene networks coordinated by hormones and delineating the neurons that regulate social behaviors.

Juntti|项目总结 我的研究计划的首要目标是了解荷尔蒙如何塑造神经 控制社会行为的途径。性腺激素是发育的关键调节因素 和成体神经功能，它们的信号导致脊椎动物的深刻差异 不同性别的生殖和攻击性行为。不同地区激素信号的差异 男性和女性可能导致神经精神疾病发病率的差异， 但他们行动的神经元和转录基础尚不清楚。这些激素可能 确定细胞的连通性、它们的活动模式或两者兼而有之。大熊猫的生殖行为 慈鱼是了解激素如何影响基因转录的理想模型系统 和神经回路功能。慈济鱼的社会行为已经被研究了近一个世纪，并且 是复杂的，但却是刻板的和可以量化的。数十种慈鱼已经被测序 基因组，我们已经在这些物种中率先进行了CRISPR基因编辑和转基因。我们 已经确定了一组对孕激素和前列腺素敏感的神经元 F2前列腺素F(F2α，前列腺素F)是产卵行为所必需的。孕激素受体(PR)信号调节 在这些细胞中的基因表达，而PGF及其受体Ptgfr是充分和必要的 开始产卵。我们试图确定Ptgfr+细胞对不同社会功能的贡献 通过对这些细胞进行基因控制的行为。《公约》 QF-QAS系统首次在慈鱼体内将允许对这些细胞和其他细胞进行研究。喜欢 其他类固醇激素受体PR作为配体激活的转录因子发挥作用。然而，它的 基因组靶标在大脑中是未知的，因此还不清楚它是如何调节行为的。我们会 确定PR如何调节慈鱼的行为惯例，并确定PR的基因组靶标 这是其行动的基础。孕激素(和其他类固醇)的产生受 下丘脑-垂体-性腺轴。感觉输入调节孕激素的产生 慈鱼：雄性气味促进其合成。我们将确定调节这一过程的细胞群 从嗅觉到内分泌系统的信号。这些方法将建立在我们之前的 调查结果和利用我们开发的技术，共同深入了解 脊椎动物的大脑对性激素进行调节和反应。这些实验将奠定一个 为理解由激素协调的基因网络和描绘 调节社会行为的神经元。