Heterogeneity of mitral cell properties determined by the timing of neurogenesis

摘要 我们有能力区分数百万种气味。每种气味都结合到以下几个子集 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投射神经元接受来自嗅觉的突触输入 神经元。二尖瓣/簇状细胞是唯一将嗅觉信息传递到嗅皮层的神经元。至 处理来自嗅觉感觉神经元的大量信息，OB投射神经元由 在功能上不同的亚群。在过去的几十年里，二尖瓣和簇状瓣膜的区别 细胞已经得到了深入的研究。此外，最近的几行证据表明，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？是什么因素(S)决定了二尖瓣细胞 房产？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？ 嗅觉信息处理中的亚群？作为一个起点，以解决我们的 知识，我们以前证明了在发育过程中不同时间产生的二尖瓣细胞是 合并到OB的功能不同的神经元回路中，这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”)分为不同的功能亚群。在这 项目中，我们将使用荧光蛋白分别标记早生成和晚生成的二尖瓣细胞 由pI开发的创新方法；宫内电穿孔质粒载体。使用这种技术，我们 将决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扮演不同的角色 通过追求以下三个特定目标进行处理：特定目标1)确定分子是否 二尖瓣细胞的表达谱随其神经发生的时间而变化；特定的目标2)表征 早期和晚期二尖瓣细胞的功能特性；以及特殊目的3)检查早期和晚期二尖瓣细胞 晚期生成的二尖瓣细胞将轴突差异地投射到嗅皮层。拟议的项目将 增进我们对S规则在嗅觉信息加工中的认识 大脑皮层。

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.