The genetic control of neuronal number and behavior

神经元数量和行为的遗传控制

基本信息

批准号：
10652437
负责人：
Jennifer Chen
金额：
$ 11.6万
依托单位：
HARVARD UNIVERSITY
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：
2022-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10652437
关键词：
Advisory Committees Affect Animals Area Behavior Behavior Control Behavioral Behavioral Genetics Brain Candidate Disease Gene Caring Cell Nucleus Cells Child Rearing Chromosome Mapping Code Compensation Control Locus Data Data Analyses Data Science Deer Mouse Detection Diagnosis Disease Drosophila genus Evolution Exhibits Experimental Genetics Fingers Genes Genetic Genomics Heritability House mice Human Hypothalamic structure Immediate-Early Genes Instinct Leadership Maps Mediating Mentors Mentorship Molecular Molecular Biology Mus Narcolepsy Nesting Behavior Neurodevelopmental Disorder Neurons Neuropeptides Optic Lobe Pathway interactions Performance Peromyscus Phenotype Population Population Sizes Primates Process Regulation Research Research Training Role Scientist Sensory Sex Behavior Sex Ratio Sister Social Behavior Specific qualifier value Stereotyping Testing Training Variant Vasopressins Work autism spectrum disorder blind candidate identification care systems career development causal variant cell type comparative comparative genomics dexterity drug development experimental study forward genetics genetic linkage analysis genetic variant genomic locus innovation neurogenetics neuropsychiatric disorder programs research and development sex sexual dimorphism skills trait

项目摘要

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.

项目摘要/摘要神经元数的遗传控制是一个重要的机制，可以通过该机制编码行为。特定神经元种群的扩展与行为创新有关嗅觉能力提高，而人类特定神经元类型的缺陷已经相关疾病包括自闭症谱系障碍。但是，指定的基因和分子途径控制行为的神经元数在很大程度上是未知的。拟议的研究调查了两种方式在下丘脑中，哪些先天行为由特定神经元的种群大小控制 Peromyscus鹿小鼠。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的数量，这是一种在社交行为中具有重要作用的神经肽。在第二个目的，我将调查特定性别的父母行为的变化如何由性别特定神经元数。这项研究利用了两种密切相关的peromyscus鹿小鼠，它们已经进化父母护理的巨大，可遗传的差异，但它们之间的遗传差异很小。首先，我会的使用比较基因组测序和神经遗传学方法，例如立即检测早期基因，暗示神经元数与神经元数量共同发展并负责的候选细胞类型 Peromyscus物种之间的行为差异。然后，通过将遗传图与单核合并测序，我将确定控制神经元种群和测试候选者的因果遗传基因座基因对神经元数和下游行为的影响。这项研究将暗示重要神经发育途径调节先天行为，并有助于我们诊断和治疗的能力神经发育疾病。拟议的研究将在Peromyscus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Sean Eddy博士。另外，我会由由凯瑟琳·杜拉克（Catherine Dulac）博士组成的咨询委员会的指导，他是社会神经源性专家行为，神经元单细胞基因组学专家史蒂夫·麦卡罗尔（Steve McCarroll）博士，博士。 Francesca Dominici和哈佛大学数据科学倡议的联合主管戴维·帕克斯（David Parkes）。在此指导下，我将发展分子生物学，小鼠行为实验和神经元单细胞数据分析的研究技能。我还将利用我的培训和参与马赛克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巧。我的研究培训和职业在一起开发活动将使我成功过渡到独立的研究科学家。