Characterization of Olfactory Bulb Projection Neuron Diversity

嗅球投射神经元多样性的表征

基本信息

批准号：
9402500
负责人：
JOHN J. NGAI
金额：
$ 22.57万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9402500
关键词：
Ablation Afferent Neurons Amygdaloid structure Anatomy Anterior Area Automobile Driving Axon Behavior Biology Brain Brain region Cells Cellular Morphology Chemicals Classification Code Cues Dendrites Development Dorsal Electrophysiology (science)Environment Financial compensation Fingerprint Foundations Future Gene Expression Gene Expression Profile Genes Genetic Genome Genomic approach Goals In Situ In Situ Hybridization Individual Instinct Interneurons Ion Channel Knowledge Label Lateral Maps Mediating Molecular Profiling Morphology Nature Nervous system structure Neurons Neurosciences Odorant Receptors Olfactory Epithelium Olfactory Pathways Olfactory tubercle Organism Pathway interactions Pattern Peripheral Physiological Population Property RNA Sensory Sensory Process Social Behavior Statistical Data Interpretation Stimulus Stream Synapses System Taxonomy Testing Validation base cell type deep sequencing differential expression entorhinal cortex experimental study learned behavior mitral cell molecular marker nerve supply neural circuit olfactory bulb olfactory nuclei olfactory sensory neurons parallel processing piriform cortex single cell sequencing tool transcriptome transcriptome sequencing

项目摘要

PROJECT SUMMARY Understanding how the nervous system extracts and encodes features of an organism’s environment is a major goal of sensory biology and systems neuroscience. In the vertebrate olfactory system, projection neurons of the main olfactory bulb receive synaptic input from the primary sensory neurons in the peripheral olfactory epithelium. These projection neurons – comprising the mitral and tufted cells – relay sensory information to multiple higher order brain centers to drive a spectrum of innate and learned behaviors. Previous studies indicate that olfactory bulb projection neurons are functionally if not genetically heterogeneous: the mitral and tufted cells are anatomically, morphologically and physiologically distinct; mitral cells can be distinguished based on their differential expression of ion channel subunits and intrinsic physiological properties; and projection neurons display different patterns of innervation in higher order olfactory centers implicated in innate and learned olfactory behaviors. One view based on this large body of evidence is that subtypes of projection neurons represent different features of the odorant stimulus and carry parallel streams of information to different olfactory centers to generate behaviors. While electrophysiological properties, expression of selected molecular markers and connectivity have been used to describe differences among projection neurons, current approaches have not yet yielded a systematic classification of olfactory bulb projection neuron diversity. This information is necessary for elucidating in a comprehensive manner the principles underlying olfactory coding as information is relayed and transformed by the population of olfactory bulb projection neurons. In the present application, we propose to apply single cell RNA profiling by deep sequencing (single cell RNA-Seq) to generate a taxonomy of olfactory bulb projection neurons. The single cell approach relies upon each cell type’s unique transcriptional signature to define itself and therefore requires no a priori knowledge of the nature or extent of diversity within the population. The taxonomy of projection neurons will be independently validated by RNA in situ hybridizations. We will further test the hypothesis that projection neurons innervating different brain regions are genetically distinct. Importantly, the identification of cell type-specific genes will allow genetic access to the newly identified cell types and the circuits in which they function. Thus we expect the proposed R21 project to enable the future development of powerful genetic tools for targeting the subcircuits mediating specific olfactory behaviors.

项目概要了解神经系统如何提取和编码有机体环境的特征是一个感觉生物学和系统神经科学的主要目标在脊椎动物的嗅觉系统中，投射。主嗅球的神经元接收来自外周初级感觉神经元的突触输入这些嗅觉上皮细胞（包括二尖瓣细胞和簇状细胞）传递感觉。信息传递到多个高级大脑中心，以驱动一系列先天和后天的行为。研究表明，嗅球投射神经元即使不是遗传异质性，也具有功能异质性：二尖瓣细胞和簇状细胞在解剖学、形态学和生理学上是不同的；根据离子通道亚基的差异表达和内在生理学来区分属性；投射神经元在高阶嗅觉中心表现出不同的神经支配模式基于大量证据的一种观点是，与先天和后天的嗅觉行为有关。投射神经元的亚型代表气味刺激的不同特征并携带平行流信息传递到不同的嗅觉中心以产生行为，而电生理特性，所选分子标记的表达和连接性已被用来描述之间的差异投射神经元，目前的方法尚未对嗅球进行系统的分类该信息对于全面阐明投影神经元多样性是必要的。基本原理嗅觉编码是由嗅觉群体传递和转换信息的在本申请中，我们建议通过深度应用单细胞RNA分析。测序（单细胞 RNA-Seq）生成嗅球投射神经元的分类。该方法依赖于每种细胞类型独特的转录特征来定义自身，因此不需要对人口多样性的性质或程度的先验知识。我们将通过 RNA 原位杂交来独立验证神经元的假设。支配不同大脑区域的投射神经元在遗传上是不同的，重要的是，它们的识别。细胞类型特异性基因将允许对新识别的细胞类型及其所在的回路进行遗传访问因此，我们期望拟议的 R21 项目能够实现强大的遗传工具的未来开发。用于针对介导特定嗅觉行为的子电路。