Cellular basis of complex social behavior

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，仍然很难从 基因组到特定的细胞群到大脑功能。在这项研究中，我们将确定如何 脊椎动物社会行为的自然变异是在基因组中编码并在大脑中执行的 通过特定细胞类型中的背景依赖性基因表达。为此，我们将利用 东非马拉维湖的慈鲷组合，利用最近的进化辐射 在最小的遗传差异下产生了巨大的社会行为差异。我们将使用新的 自动化的方法来量化男性凉亭建设行为的差异。我们将绘制前脑细胞 在建造凉亭期间招募的类型，并确定这些大脑区域的顺式调节回路，使用 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），以确定鲍尔行为的遗传基础，并将基因组区域与 特定的行为和细胞子程序。这项工作将确定细胞群，基因表达 程序和神经元回路调节社会行为，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。

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.