Cellular basis of complex social behavior

复杂社会行为的细胞基础

基本信息

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
项目类别：
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

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

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项目摘要

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，包括发展，生理和疾病。对于复杂的行为，很难从特定细胞群体到脑功能的基因组。在拟议的研究中，我们将确定脊椎动物社会行为的自然变化在基因组中编码并在大脑中执行通过上下文依赖基因表达在特定细胞类型中。为此，我们将利用来自东非马拉维湖的丽鱼科的集合，以利用最近的进化辐射通过最小的遗传差异，这在社会行为上产生了巨大差异。我们将使用新的自动化方法来量化男性凉亭的差异。我们将绘制前脑细胞鲍尔建筑物期间招募的类型，并使用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映射和构造近乎异构的线（尼尔），以确定鲍尔行为的遗传基础，并将基因组区域联系起来特定的行为和细胞子例程。这项工作将识别细胞群体，基因表达程序和神经元电路调节杂种脊椎动物中的社会行为并提供对人类行为多样性的比较见解，包括常见的神经系统疾病。