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 |项目摘要 我的研究计划的总体目标是了解激素如何塑造中性 控制社会行为的途径。性腺激素是发展的主要调节因子 和成人神经功能及其信号传导导致脊椎动物动物的巨大差异 性别跨性别的生殖和侵略性行为。骑马信号的差异 男人和女人可能会导致神经精神疾病发病率的差异， 但是，其行为的神经元和转录基础尚不清楚。这些恐怖可能 确定细胞的连通性，它们的活性模式或两者兼而有之。生殖行为 丽鱼科鱼是了解激素如何影响基因转录的理想模型系统 和神经电路功能。丽鱼科学的社会行为已经研究了近一个世纪，并且 是复杂的，但刻板印象和可量化。数十种丽鱼科生物已经测序 基因组，我们已经开创了CRISPR基因编辑和这些物种中的转基因。我们 已经确定了对马的孕激素和前列腺素敏感的神经元种群 F2α（PGF）对于产卵行为至​​关重要。孕激素受体（PR）信号传导调节 这些细胞中的基因表达，而PGF及其接收器PTGFR足以且必要 启动产卵。我们试图确定PTGFR+细胞对各种社会的贡献 通过对这些细胞的一般定向操纵的行为。实施 在丽鱼科学的QF-Quas系统中，QF-Quas系统将允许研究这些和其他细胞。喜欢 其他类固醇马酮受体，PR充当配体激活的转录因子。但是，它 基因组靶标在大脑中不知道，因此尚不清楚它如何调节行为。我们将 确定PR如何调节丽鱼科行为常规并确定PR的基因组靶标 这是其行动的基础。孕激素（和其他类固醇）的产生由 下丘脑 - 垂体 - 基达轴。感觉输入调节孕激素的产生 丽鱼科：雄性气味促进其合成。我们将确定调解这种情况的细胞组 从嗅觉到内分泌系统的信号传导。这些方法将基于我们以前的 发现和利用我们已经开发的技术，共同提供了有关如何 脊椎动物的大脑调节和反应性激素。这些实验将放置 理解由激素协调的基因网络的基础，并描述 调节社会行为的神经元。