The genetic control of neuronal number and behavior

项目概要/摘要 神经元数量的遗传控制是基因编码行为的重要机制。 特定神经元群体的扩张与行为创新有关， 嗅觉能力增强，而人类特定神经元类型的缺乏与 包括自闭症谱系障碍在内的疾病。然而，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。拟议的研究调查了两种方法， 哪些先天行为是由下丘脑中特定神经元的数量控制的？ 鹿鼠在第一个目标中，我将研究如何控制父母筑巢行为的变化 通过表达加压素的神经元数量，加压素是一种在社会性行为中起重要作用的神经肽。在 第二个目标，我将研究性别特异性父母行为的变化是如何被性别特异性控制的。 神经元数量 这项研究利用了两种密切相关的鹿鼠， 在父母照顾方面存在巨大的、可遗传的差异，但它们之间的遗传差异极小。首先我会 使用比较基因组测序和神经遗传学方法，如检测即刻- 早期基因，暗示候选细胞类型的神经元数量是共同进化的，并负责 不同种属的行为差异。然后，通过结合遗传作图和单核 测序，我将确定控制神经元群体大小的因果遗传位点，并测试候选人。 基因对神经元数量和下游行为的影响。这项研究将涉及重要的 调节先天行为的神经发育途径，有助于我们诊断和治疗 神经发育疾病 这项拟议中的研究将在Peromyscus专家Hopi Hoekstra博士的指导下进行 行为遗传学和肖恩·埃迪博士，一位比较基因组数据分析专家。另外，我将 由凯瑟琳迪拉克博士组成的咨询委员会指导，她是社会神经遗传学专家， 神经元单细胞基因组学专家Steve McCarroll博士和Francesca Dominici博士以及 大卫帕克斯，联合主任的哈佛数据科学倡议。在这种指导下，我将发展 在分子生物学，小鼠行为实验和神经元单细胞数据分析的研究技能。我 我还将利用我在MOSAIC项目中的培训和参与来发展领导技能，包括实验室 管理，包容性的指导，和科学的演讲技巧。我的研究训练和职业生涯 发展活动将使我成功地过渡到一名独立的研究科学家。

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.