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，对气味特征的基本了解是由大脑解码的，以及如何有关这些功能的信息仍然缺乏嗅觉系统。感觉有气味通过嗅觉上皮表达专用气味受体的嗅觉感觉神经元（OSN）（ORS）。每个OSN以数百或基因的物种依赖性补体表示一个或基因。表达相同或类型的OSN轴突会收敛到嗅球上的相同肾小球（OB）表面，形成一个2D地图，在个人之间大致刻板印象。二尖瓣/簇细胞（MTC）， 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将其轴突发送到较高的嗅觉加工中心，形成通常假定的轴突高度分布和主要随机投影模式。嗅觉处理的计算模型是对MTC Projectome的结构敏感，其不同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基础的计算原理。但是，迄今为止这些个人的这些预测的结构仍然是未知的领域，以及有关统计的信息每个人的单个MT神经元的合奏的预测非常有限，尤其是在哺乳动物中。这是由于基于成像的解剖重建策略的产量低，通过稀疏标记每个大脑的个别神经元数。要了解MTC Projectome的逻辑和特异性，在此中项目，我们将利用最新测序技术的高吞吐量，例如荧光原位测序（FISSEQ）和基于新型的RNA条形码测序方法（MAPSEQ）连词具有体内功能成像，现代计算技术和理论工具。初步数据包括数百个单个神经元的大脑范围的投影支持存在可以比较动物之间的专门非随机投影基序。我们将进一步调查大脑范围的MTC投影的结构与MTC对大量气味剂的响应相关联。我们将与更广泛的嗅觉社区共享此数据，并将其纳入计算网络嗅觉处理的模型。该项目的具体目的（SAS）是：SA1。确定逻辑和嗅觉的主要目标大脑区域的单个二尖瓣和簇细胞的投影的特异性电灯泡。 SA2。研究二尖瓣和簇细胞在单个OB靶向大脑中的射击的结构地区。 SA3。了解灯泡Projectome与二尖瓣的气味响应之间的关系和簇状细胞。