Understanding the Logic of the Brain-Wide Olfactory Bulb Projectome

总结 到目前为止，对大脑解码气味的哪些特征以及如何解码的基本理解， 关于这些特征通过嗅觉系统传导的信息仍然缺乏。气味被感知 通过嗅上皮中表达特异性气味受体的嗅觉感觉神经元（OSNs） （OR）。每个OSN表达一个OR基因的数百个OR基因的物种依赖性互补。 表达相同OR类型的OSN轴突会聚到嗅球（OB）上的相同肾小球上 表面，形成一个2D地图，这是近似刻板的个人。二尖瓣/簇状细胞（MTCs）， OB的主要神经元由来自肾小球的输入以及侧向和自上而下的信号驱动。 MTC将轴突发送到更高的嗅觉处理中心，形成通常认为是， 高度分布和很大程度上随机的投影模式。嗅觉处理的计算模型是 对MTC投影图的结构敏感，不同的模型依赖于不同的 连接.因此，确定MTC连接性的结构对于以下方面是至关重要的： 理解嗅觉信息处理的计算原理。然而，迄今为止， 这些预测在个人之间的结构仍然是未知的领域， 单个MT神经元的集合预测是非常有限的，特别是在哺乳动物中。这是 由于通过对小的图像进行稀疏标记的基于成像的解剖重建策略的低产量 每个大脑的单个神经元数量。为了理解MTC项目的逻辑和特殊性，在此 项目，我们将利用最先进的测序技术的高通量，如荧光 原位测序（FISSEQ）和基于RNA条形码测序的新方法（MAPseq）相结合 利用体内功能成像、现代计算技术和理论工具。初步数据 由数百个单个神经元组成的全脑投射支持了 可以在动物之间进行比较的专门的、非随机的投射图案。我们将进一步调查 的结构，脑范围内的MTC的预测，并将其与MTC的反应，以大套气味。 我们将与更广泛的嗅觉社区分享这些数据，并将其纳入计算网络 嗅觉加工模型该项目的具体目标（SA）是：SA 1。为了确定逻辑和 单个僧帽细胞和簇状细胞在嗅觉主要靶脑区投射的特异性 灯泡SA 2.目的：观察OB靶脑内二尖瓣和簇状细胞投射结构 地区SA 3.了解二尖瓣球突与气味反应的关系 和簇状细胞。

SUMMARY To date, fundamental understanding of which features of odorants are decoded by the brain, and how information about these features is channeled through the olfactory system is still lacking. Odorants are sensed by the olfactory sensory neurons (OSNs) in the olfactory epithelium expressing specialized odorant receptors (ORs). Each OSN expresses one OR gene out of a species-dependent complement of hundreds of OR genes. OSN axons expressing the same OR type converge onto the same glomerulus on the olfactory bulb (OB) surface, forming a 2D map which is approximately stereotypical across individuals. Mitral/tufted cells (MTCs), the principal neurons of the OB are driven by inputs from glomeruli, as well as lateral and top-down signals. MTCs send their axons to higher olfactory processing centers, forming what is commonly assumed to be, highly distributed and largely random projection patterns. Computational models of olfactory processing are sensitive to the structure of the MTC projectome, with different models relying on different statistics of connections. Determining the structure of MTC connectivity is therefore of utmost importance for understanding the computational principles underlying olfactory information processing. However, to date, the structure of these projections across individuals remains uncharted territory, and information on the statistics of projections for ensembles of single MT neurons per individual is very limited, especially, in mammals. This is due to the low yield of imaging-based anatomical reconstruction strategies via sparse labeling of a small number of individual neurons per brain. To understand the logic and specificity of the MTC projectome, in this project, we will leverage the high throughput of state-of-the-art sequencing technologies, such as fluorescence in situ sequencing (FISSEQ) and a novel RNA barcoding sequencing-based method (MAPseq) in conjunction with in vivo functional imaging, modern computational technologies and theoretical tools. Preliminary data comprising of the brain-wide projections of hundreds of individual neurons supports the existence of specialized, non-random projection motifs that can be compared between animals. We will further investigate the structure of the brain-wide MTC projections and relate it to the MTC responses to large sets of odorants. We will share this data with the broader olfaction community and incorporate it into a computational network model of olfactory processing. The Specific Aims (SAs) of this project are: SA1. To determine the logic and specificity of individual mitral and tufted cells projections across the major target brain regions of the olfactory bulb. SA2. To investigate the structure of mitral and tufted cells' projectome within individual OB target brain regions. SA3. To understand the relationship between the bulb projectome and the odor responses of mitral and tufted cells.