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

• 批准号: 10200750
• 负责人: Fumiaki Imamura
• 金额: $ 32.93万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200750
• 关键词: Address; Alzheimer' s Disease; Anatomy; Axon; Binding; Biophysics; Brain; Cells; Development; Elderly; Electroporation; Fluorescence-Activated Cell Sorting; Food; Generations; Goals; Heterogeneity; Histologic; Image; Imaging Techniques; In Vitro; Knowledge; Label; Life; Maps; Methods; Molecular; Neurodegenerative Disorders; Neurons; Odors; Olfactory Cortex; Olfactory Epithelium; Olfactory Pathways; Olfactory dysfunction; 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

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.

摘要 我们有能力区分数百万种气味。每一种气味都与 嗅觉感觉神经元，其随后激活嗅球（OB）中的特定肾小球。在 肾小球、僧帽细胞和簇状细胞，OB投射神经元，接受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，二尖瓣和簇状之间的差异 细胞已经被深入研究。此外，最近的一些证据表明，我们不能认为， 二尖瓣细胞不再是一个单一的群体。然而，二尖瓣细胞的最基本方面 异质性仍然是未知的：有多少二尖瓣细胞亚群？什么因素决定了二尖瓣细胞 属性？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一个起点，解决这些重大差距， 知识，我们以前证明，二尖瓣细胞产生在不同的时间在发展过程中， 整合到OB中功能不同的神经元回路中，这表明我们可以将二尖瓣细胞 根据它们的神经发生时间（"神经元出生日期"）将它们分成功能不同的亚组。在这 项目，我们将分别标记早期和晚期产生的二尖瓣细胞与荧光蛋白使用 PI开发的创新方法;质粒载体的子宫内电穿孔。利用这项技术，我们 将确定不同神经元出生日期的二尖瓣细胞是否在嗅觉信息中扮演不同的角色 通过追求以下三个具体目标进行处理：具体目标1）确定分子是否 二尖瓣细胞的表达谱基于其神经发生的时间而变化;具体目的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）检查早期和晚期生成的二尖瓣细胞是否 晚期产生的二尖瓣细胞差异性地将轴突投射到嗅觉皮层。拟议项目将 推进我们对规则的知识用于嗅觉信息处理的OB和嗅觉 皮层