Cellular basis of complex social behavior

复杂社会行为的细胞基础

• 批准号: 10701800
• 负责人: Jeffery Todd Streelman
• 金额: $ 36.18万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-09 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10701800
• 关键词: 3-Dimensional; ATAC-seq; Acute; Affect; Africa; Alleles; Anatomy; Animals; Behavior; Behavioral; Behavioral Assay; Brain; Brain Diseases; Brain region; Cell Nucleus; Cells; Cichlids; Complex; Coupled; Courtship; DNA Resequencing; Development; Disease; Epigenetic Process; Female; Gene Expression; Gene Expression Profiling; Generations; Genes; Genetic; Genetic Drift; Genetic Variation; Genome; Genome Mappings; Genomic approach; Genomics; Goals; Human; Hybrids; Individual; Instinct; Knowledge; Link; Malawi; Maps; Mediating; Mental Depression; Methods; Modeling; Molecular; Neurons; Partner in relationship; Pathologic; Pattern; Phenotype; Physiology; Population; Prosencephalon; Quantitative Trait Loci; Radiation; Reagent; Research; Shapes; Signal Transduction; Silicon Dioxide; Social Behavior; Specific qualifier value; Structure; System; Time; Variant; Vertebrates; Work; brain cell; cell type; comparative; experimental study; fitness; genetic variant; genomic locus; insight; invention; male; nervous system disorder; neural; neural circuit; neuronal circuitry; novel strategies; programs; recruit; single-cell RNA sequencing; social; success; trait; transcriptome sequencing

Summary/Abstract A broad goal for biologists is to understand how genetic variation influences phenotype, including development, physiology, and disease. For complex behaviors, it remains difficult to trace a path from the genome to particular cell populations to brain function. In the proposed research, we will identify how natural variation in vertebrate social behavior is encoded within the genome and executed in the brain via context dependent gene expression in specific cell types. To accomplish this, we will utilize the assemblage of cichlids from Lake Malawi, East Africa to take advantage of recent evolutionary radiation that generated large differences in social behavior with minimal genetic divergence. We will use new automated methods to quantify differences in male bower building behavior. We will map forebrain cell types recruited during bower building and identify cis-regulatory circuits in these brain regions, using RNA-seq and ATAC-seq from single cells. Finally, we will use QTL mapping and the construction of near-isogenic lines (NILs) to identify the genetic basis of bower behavior and link genome regions to specific behavioral and cellular subroutines. This work will identify cell populations, gene expression programs and neuronal circuits regulating social behaviors in outbred vertebrates and provide comparative insights into human behavioral diversity including common neurological diseases.

摘要/摘要 生物学家的一个广泛目标是了解遗传变异如何影响表型，包括 发育、生理和疾病。对于复杂的行为，仍然很难追踪其路径 基因组到特定细胞群到大脑功能。在拟议的研究中，我们将确定如何 脊椎动物社会行为的自然变异在基因组中编码并在大脑中执行 通过特定细胞类型中上下文相关的基因表达。为了实现这一目标，我们将利用 来自东非马拉维湖的丽鱼科鱼群，利用最近的进化辐射 这在遗传差异最小的情况下产生了巨大的社会行为差异。我们将使用新的 量化男性凉亭建筑行为差异的自动化方法。我们将绘制前脑细胞图 使用在建造凉亭期间招募的类型并识别这些大脑区域中的顺式调节电路 来自单细胞的 RNA-seq 和 ATAC-seq。最后，我们将使用QTL作图和构建 近等基因系（NIL），用于识别凉亭行为的遗传基础并将基因组区域与 特定的行为和细胞子程序。这项工作将鉴定细胞群、基因表达 调节远交脊椎动物社会行为的程序和神经元回路并提供 对人类行为多样性（包括常见神经系统疾病）的比较见解。