Understanding the logic of the brain-wide olfactory bulb projectome

了解全脑嗅球投射组的逻辑

基本信息

批准号：
10378557
负责人：
Dinu Florentin ALBEANU
金额：
$ 90.47万
依托单位：
COLD SPRING HARBOR LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-15 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10378557
关键词：
Address Age Anatomy Animals Anterior Area Axon Bar Codes Behavior Brain Brain region Breathing Bypass Cells Communities Complement Computer Models Data Detection Dorsal Fire - disasters Fluorescence Food Foundations Functional Imaging Gases Human Image Individual Information Retrieval Label Lasers Lateral Location Logic Mammals Maps Medial Methods Microdissection Modeling Modernization Monitor Multiplexed Analysis of Projections by Sequencing Nature Neurons Neurosciences Odorant Receptors Odors Olfactory Epithelium Olfactory Pathways Olfactory tubercle Parents Pattern Preparation Process Quality of life RNA Receptor Gene Research Scanning Sensory Signal Transduction Sister Slice Smell Perception Specificity Structure Surface Technology Testing Thalamic structure Theoretical Studies Therapeutic Thinness awake base computational network modeling data sharing image registration in situ sequencing in vivo information processing insight interest neuronal cell body novel olfactory bulb olfactory nuclei olfactory sensory neurons piriform cortex prevent reconstruction response sensory system statistics tool two-photon

项目摘要

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.

概括迄今为止，人们对大脑解码气味剂的哪些特征以及如何解码有了基本的了解有关这些特征通过嗅觉系统传递的信息仍然缺乏。感知到气味由嗅觉上皮细胞中表达特殊气味受体的嗅觉感觉神经元 (OSN) 产生（或）。每个 OSN 表达数百个 OR 基因的物种依赖性互补序列中的一个 OR 基因。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，形成一个二维地图，该地图在个体之间大致具有刻板印象。二尖瓣/簇状细胞（MTC）， OB 的主要神经元由肾小球的输入以及横向和自上而下的信号驱动。 MTC 将它们的轴突发送到更高的嗅觉处理中心，形成通常假设的，高度分布且很大程度上随机的投影模式。嗅觉处理的计算模型是对 MTC 投影组的结构敏感，不同的模型依赖于不同的统计数据连接。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，迄今为止，这些对个人的预测结构仍然是未知领域，有关统计数据的信息对每个个体的单个 MT 神经元集合的预测非常有限，特别是在哺乳动物中。这是由于通过小块的稀疏标记基于成像的解剖重建策略的产量低每个大脑的单个神经元的数量。要了解 MTC 项目组的逻辑和特殊性，在此项目中，我们将利用最先进的测序技术的高通量，例如荧光原位测序 (FISSEQ) 和基于 RNA 条形码的新型测序方法 (MAPseq) 相结合具有体内功能成像、现代计算技术和理论工具。初步数据由数百个单个神经元的全脑投射组成，支持以下观点的存在：可以在动物之间进行比较的专门的、非随机的投影图案。我们将进一步调查全脑 MTC 预测的结构，并将其与 MTC 对大量气味的反应联系起来。我们将与更广泛的嗅觉界分享这些数据，并将其纳入计算网络嗅觉处理模型。该项目的具体目标 (SA) 是：SA1。确定逻辑和单个二尖瓣和簇状细胞在嗅觉主要目标大脑区域的投射的特异性电灯泡。 SA2。研究个体 OB 靶脑内二尖瓣和簇状细胞投射组的结构地区。 SA3。了解灯泡投射组与二尖瓣气味反应之间的关系和簇状细胞。