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Heterogeneity of mitral cell properties determined by the timing of neurogenesis

由神经发生时间决定的二尖瓣细胞特性的异质性

基本信息

批准号：
9363291
负责人：
Fumiaki Imamura
金额：
$ 33.69万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9363291
关键词：
Address Alzheimer&apos s Disease Anatomy Axon Binding Biophysics Brain Cells Development Elderly Electroporation Fluorescence-Activated Cell Sorting Food Functional disorder Generations Goals Heterogeneity Histologic Image Analysis Imaging Techniques In Vitro Knowledge Label Life Maps Methods Molecular Molecular Profiling Neurodegenerative Disorders Neurons Odors Olfactory Cortex Olfactory Epithelium Olfactory Pathways Parkinson Disease Pathologic Patients Pattern Plasmid Cloning Vector Play Population Process Production Property Proteins Research Role Sensory Process Slice Smell Perception Subgroup Synapses Techniques Testing TimeLine Width base common symptom experimental study genome-wide in utero in vivo calcium imaging information processing innovation insight mitral cell neural circuit neurogenesis neuronal circuitry novel olfactory bulb olfactory sensory neurons patch clamp piriform cortex response tomography transcription factor transcriptome transcriptome sequencing transmission process two-photon

项目摘要

ABSTRACT We have an ability to discriminate between millions of odors. Each odorant binds to subsets of olfactory sensory neurons, which subsequently activate specific glomeruli in the olfactory bulb (OB). In the glomeruli, mitral and tufted cells, OB projection neurons, receive synaptic inputs from the olfactory sensory neurons. Mitral/tufted cells are the only neurons that transmit olfactory information to the olfactory cortex. To process the vast amount of information from the olfactory sensory neurons, OB projection neurons consist of functionally different subpopulations. Over the past several decades, differences between mitral and tufted cells have been intensively studied. Moreover, several lines of recent evidence show that we cannot consider mitral cells as a homogeneous population anymore. However, the most fundamental aspects of mitral cell heterogeneity are still unknown: How many mitral cell subpopulations? What factor(s) determines the mitral cell properties? Are there correlations among different mitral cell properties? What are the roles of each mitral cell subpopulation in olfactory information processing? As a starting point to address these significant gaps in our knowledge, we previously demonstrated that mitral cells generated at different timing during development were incorporated into functionally distinct neuronal circuits in the OB, suggesting that we can sort the mitral cells into functionally different subgroups based on their timing of neurogenesis (“neuronal birthdate”). In this project, we will separately label the early- and late-generated mitral cells with fluorescent proteins using an innovative method developed by the PI; in utero electroporation of plasmid vectors. Using this technique, we will determine whether mitral cells with different neuronal birthdates play different roles in olfactory information processing by pursuing following three specific aims: Specific Aim 1) Determine whether the molecular expression profile of mitral cells varies based on their timing of neurogenesis; Specific Aim 2) Characterize the functional properties of early- and late-generated mitral cells; and Specific Aim 3) Examine whether early- and late-generated mitral cells differentially project axons to the olfactory cortex. The proposed project will advance our knowledge about rule(s) used for olfactory information processing in the OB and the olfactory cortex.

抽象的我们有能力区分数百万种气味。每种气味剂都与以下子集结合嗅觉感觉神经元，随后激活嗅球 (OB) 中的特定肾小球。在肾小球、二尖瓣和簇状细胞、OB 投射神经元接收来自嗅觉感觉的突触输入神经元。二尖瓣/簇状细胞是唯一将嗅觉信息传递到嗅觉皮层的神经元。到处理来自嗅觉感觉神经元的大量信息，OB 投射神经元包括功能不同的亚群。在过去的几十年里，二尖瓣和簇绒之间的差异细胞已被深入研究。此外，最近的一些证据表明我们不能考虑二尖瓣细胞不再是同质群体。然而，二尖瓣细胞最基本的方面异质性仍然未知：有多少二尖瓣细胞亚群？二尖瓣细胞由什么因素决定特性？不同的二尖瓣细胞特性之间是否存在相关性？每个二尖瓣细胞的作用是什么嗅觉信息处理的亚群？作为解决我们的这些重大差距的起点根据知识，我们之前证明二尖瓣细胞在发育过程中的不同时间产生纳入 OB 中功能不同的神经元回路，表明我们可以对二尖瓣细胞进行分类根据神经发生的时间（“神经元出生日期”）分为功能不同的亚组。在这个项目中，我们将使用荧光蛋白分别标记早期和晚期生成的二尖瓣细胞 PI 开发的创新方法；质粒载体的子宫内电穿孔。使用这种技术，我们将确定具有不同神经元出生日期的二尖瓣细胞是否在嗅觉信息中发挥不同的作用通过追求以下三个特定目标进行处理：具体目标 1) 确定分子是否二尖瓣细胞的表达谱根据其神经发生的时间而变化；具体目标 2) 表征早期和晚期生成的二尖瓣细胞的功能特性；和具体目标 3) 检查是否早期和晚期产生的二尖瓣细胞将轴突差异性地投射到嗅觉皮层。拟议的项目将增进我们对 OB 和嗅觉中嗅觉信息处理规则的了解皮质。