Understanding the logic of the brain-wide olfactory bulb projectome

摘要 到目前为止，基本了解气味的哪些特征是由大脑解码的，以及如何 关于这些特征的信息是通过嗅觉系统传递的，目前还缺乏。气味是可以感觉到的 通过嗅觉上皮中表达特殊气味受体的嗅觉神经元 (ORS)。每个OSN表达数百个OR基因中与物种相关的一个OR基因。 表达相同OR类型的OSN轴突汇聚到嗅球上的同一小球(OB) 表面，形成一个2D地图，这几乎是个人的刻板印象。二尖瓣/簇状细胞(MTCs)， OB的主要神经元由肾小球的输入以及侧向和自上而下的信号驱动。 MTC将它们的轴突送到高级嗅觉处理中心，形成通常认为的， 高度分布且在很大程度上随机的投影图案。嗅觉处理的计算模型有 对MTC项目组的结构敏感，不同的模型依赖于不同的统计数据 关系。因此，确定MTC连接的结构对于 了解嗅觉信息处理的计算原理。然而，到目前为止， 这些个人预测的结构仍然是未知的领域，关于 对每个个体单个MT神经元集合的投射非常有限，特别是在哺乳动物中。这是 由于基于成像的解剖重建策略通过稀疏标记的小的 每个大脑中单个神经元的数量。要了解MTC项目组的逻辑和特殊性，请参阅 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)和一种新的基于RNA条码测序的方法(MAPSEQ) 利用活体功能成像、现代计算技术和理论工具。初步数据 由数百个单个神经元的全脑投射组成，支持 可以在动物之间进行比较的特殊的、非随机的投影图案。我们将进一步调查 整个大脑MTC投射的结构，并将其与MTC对大组气味的反应联系起来。 我们将与更广泛的嗅觉社区共享这些数据，并将其整合到计算网络中 嗅觉加工模型。本项目的具体目标(SA)是：SA1。要确定逻辑与 单个二尖瓣和簇状细胞在嗅觉主要靶区投射的特异性 灯泡。SA2.单侧OB靶脑内二尖瓣和簇状细胞投射组结构的研究 地区。SA3.了解二尖瓣球囊投影组与气味反应的关系 和簇生的细胞。

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.