The genetic control of neuronal number and behavior

项目摘要/摘要 神经元数量的遗传控制是基因对行为进行编码的重要机制。 特定神经元群体的扩展与行为创新有关，例如 嗅觉能力增强，而人类特定神经元类型的缺陷与 患有包括自闭症谱系障碍在内的障碍。然而，指定的基因和分子途径 控制行为的神经元数量在很大程度上是未知的。这项拟议的研究以两种方式调查了 哪些先天行为是由下丘脑中特定神经元的群体大小控制的 梅花鹿小白鼠。在第一个目标中，我将调查父母筑巢行为的差异是如何被控制的 通过大量神经元表达加压素，这是一种在社会性行为中起重要作用的神经肽。在……里面 第二个目标，我将调查不同性别的父母行为的差异是如何受到不同性别的控制的 神经元数量。 这项研究利用了两种近缘的Permyscus鹿小鼠，这两种小鼠已经进化成 在父母照顾方面有很大的、可遗传的差异，但它们之间的遗传差异很小。首先，我会 使用比较基因组测序和神经遗传学方法，例如检测即刻- 早期基因，以暗示其神经元数量与其共同进化并负责的候选细胞类型 Permyscus物种间的行为差异。然后，通过将遗传作图与单核相结合 测序，我将确定控制神经元种群大小的因果遗传基因座并测试候选 影响神经元数量和下游行为的基因。这项研究将牵涉到重要的 神经发育途径调节先天行为并有助于我们的诊断和治疗能力 神经发育疾病。 拟议的研究将在Permyscus专家Hopi Hoekstra博士的指导下进行 行为遗传学和比较基因组数据分析专家肖恩·埃迪博士。另外，我还会 由凯瑟琳·杜拉克博士组成的咨询委员会提供指导，该委员会是一位社会遗传学方面的专家 行为，神经细胞单细胞基因组学专家Steve McCarroll博士和Francesca Dominici博士和 哈佛数据科学倡议联席主任大卫·帕克斯说。在这个导师的指导下，我将发展 具备分子生物学、小鼠行为实验和神经元单细胞数据分析方面的研究技能。我 我还将利用我的培训和参与MOSAIC计划来发展领导技能，包括实验室 管理、包容性指导和科学演示技能。总而言之，我的研究培训和职业生涯 开发活动将启动我向独立研究科学家的成功过渡。

Project Summary/Abstract The genetic control of neuron number is an important mechanism by which genes can encode for behavior. Expansions of specific neuronal populations have been associated with behavioral innovations such as increased olfactory abilities, while deficiencies of particular neuronal types in humans have been associated with disorders including autism spectrum disorder. However, the genes and molecular pathways that specify neuron number to govern behavior are largely unknown. The proposed research investigates two ways in which innate behaviors are controlled by population sizes of specific neurons in the hypothalamus of Peromyscus deer mice. In the first aim, I will investigate how variation in parental nesting behavior is controlled by numbers of neuron expressing vasopressin, a neuropeptide with important roles in sociosexual behavior. In the second aim, I will investigate how variation in sex-specific parental behaviors are controlled by sex-specific neuronal numbers. This research takes advantage of two closely-related species of Peromyscus deer mice which have evolved large, heritable differences in parental care, but have minimal genetic differences between them. First, I will use comparative genomic sequencing and neurogenetics approaches, such as the detection of immediate- early genes, to implicate candidate cell types whose neuron numbers are co-evolving with and responsible for behavioral differences across Peromyscus species. Then, by combining genetic mapping with single-nuclei sequencing, I will determine the causal genetic loci controlling neuronal population sizes and test candidate genes for their effect on neuron number and downstream behavior. This research will implicate important neurodevelopmental pathways regulating innate behavior and contribute to our ability to diagnose and treat neurodevelopmental diseases. The proposed research will be conducted under the mentorship of Dr. Hopi Hoekstra, an expert in Peromyscus behavioral genetics, and Dr. Sean Eddy, an expert in comparative genomic data analysis. Additionally, I will be mentored by an advisory committee composed of Dr. Catherine Dulac, an expert in neurogenetics of social behaviors, Dr. Steve McCarroll, an expert in neuronal single-cell genomics, and Drs. Francesca Dominici and David Parkes, co-directors of the Harvard Data Science Initiative. Under this mentorship, I will develop research skills in molecular biology, mouse behavioral experiments, and neuronal single-cell data analysis. I will also use my training and participation in the MOSAIC program to develop leadership skills including lab management, inclusive mentoring, and scientific presentation skills. Together, my research training and career development activities will launch my successful transition to an independent research scientist.