Olfactory Bulb Local Circuits

嗅球局部电路

基本信息

批准号：
10374882
负责人：
Charles A Greer
金额：
$ 35.59万
依托单位：
YALE UNIVERSITY
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：
2019-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10374882
关键词：
3-Dimensional Activities of Daily Living Address Adult Affect Age Amacrine Cells Apical Attention Axodendritic Synapse Axon Back Basal Cell Biophysics Brain Cell Lineage Cells Characteristics Code Complement Data Dendrites Dendritic Spines Dendrodendritic Synapse Development Electron Microscopy Electroporation Embryo FOS gene Foundations Genetic Recombination Goals Immunoelectron Microscopy Individual Interneurons Label Ligand Binding Light Literature Maps Mediating Molecular Morphology Mus Nervous system structure Neurons Odorant Receptors Odors Olfactory Epithelium Olfactory Pathways Perinatal Phenotype Plasmids Population Population Projection Procedures Process Property Proteins Recording of previous events Regulation Reporting Research Retinal Ganglion Cells Role Series Shapes Smell Perception Spatial Distribution Specificity Synapses Synaptic Vesicles Tamoxifen Techniques Testing Thymidine Visual Pathways Work analog base experimental study fluorophore granule cell immunohistochemical markers in utero innovation insight light microscopy mitral cell neural circuit neurogenesis neuronal cell body novel strategies olfactory bulb olfactory bulb glomeruli olfactory sensory neurons postnatal receptor reconstruction sensory system sound stem cells synaptic function synaptogenesis systematic review

项目摘要

Project Summary – Abstract The perception of odors begins in the olfactory epithelium when odorant ligands bind on olfactory sensory neurons, each of which expresses only 1 of ~1200 candidate receptors. Axons coming from neurons expressing the same odorant receptor converge into only 2/3 glomeruli/olfactory bulb where they synapse onto projection neurons, each of which innervates a single glomerulus. Deep to the glomeruli, within the external plexiform layer (EPL), odor coding is tuned by local synaptic circuits. Deciphering connectivity with the EPL is the first step toward understanding the mechanisms of central odor processing. Several hypotheses of local processing within the EPL have been proposed and its synaptic organization is often presented as canonical. However, we lack a fundamental understanding of the how the diversity in interneuron, granule cell (GC), structural, molecular, and topographical organization affects EPL local circuits, which is an impediment to interpreting functional studies. Here we propose a series of testable hypotheses and experiments on factors that may influence the organization of GCs and their local synaptic circuits. These studies build on our prior developmental and ultrastructural work as well as a systematic review of the current literature and the recognition that fundamental features of EPL organization and connectivity have been presumed, but not empirically tested. First, we propose to address the hypotheses that the clonal history, timing and order of GC neurogenesis are determinants of their organization/distribution in the olfactory bulb. Using multiple strategies to track neurogenesis, cell lineage/fate we will assess the spiny dendritic arbors of GCs beginning in the embryo and continuing at regular intervals to those generated up 200 days of age. In addition, and not among prior studies, we propose to carefully assess the organization of the GC basal dendrites which are the primary recipients of incoming centrifugal modulation (Rothermei and Wachowiak, 2014; Kapoor et al., 2016; de Almeida et al., 2015). Second, we propose to test the hypothesis that the synaptology and molecular features of the dendrodendritic synapses in the EPL vary as a function of age. Presently, little is known of the structural features that regulate dendrodendritic synapses or how the molecular properties of the mitral to GC and the reciprocal GC to mitral cell synapses may differ. The analyses will address that fundamental problem and provide a sound foundation for the interpretation of functional analyses of odor processing. In addition, we will address the spatial distribution of synaptic appositions along 2o dendrites and the degree to which the features of the synaptic specialization change with age. Because the questions we propose to address are important throughout the nervous system, we anticipate that the results will have broad implications for understanding targeting, laminar specificity, and synaptic connectivity of neurons throughout the brain.

项目总结 – 摘要当气味配体与嗅觉结合时，气味的感知开始于嗅觉上皮感觉神经元，每个神经元仅表达来自约 1200 个候选轴突中的 1 个。表达相同气味受体的神经元仅汇聚到 2/3 肾小球/嗅球，其中它们突触到投射神经元，每个神经元都支配单个肾小球深处。在肾小球的外部丛状层 (EPL) 内，气味编码由局部突触电路调节。破译与 EPL 的连接是理解中枢机制的第一步已经提出了 EPL 内的局部处理的几种假设及其结果。突触组织通常被认为是规范的，但是我们缺乏对突触组织的基本理解。中间神经元、颗粒细胞 (GC)、结构、分子和拓扑结构的多样性如何组织影响 EPL 局部电路，这是解释功能研究的障碍。一系列可检验的假设和实验提出了可能影响组织的因素这些研究建立在我们之前的发育和局部突触回路的基础上。超微结构工作以及对当前文献的系统回顾和认识 EPL 组织和连接性的基本特征已被推测，但并非凭经验得出首先，我们建议解决 GC 的克隆历史、时间和顺序的假设。神经发生是嗅球组织/分布的决定因素。跟踪神经发生、细胞谱系/命运的策略我们将评估 GC 的多刺树突乔木从胚胎开始，定期持续到 200 天龄。此外，我们建议仔细评估 GC 基础的组织，而不是在之前的研究中树突是传入离心调制的主要接受者（Rothermei 和 Wachowiak，2014；Kapoor 等，2016；de Almeida 等，2015）。假设 EPL 中树突状突触的突触学和分子特征有所不同目前，人们对调节树突状结构的结构特征知之甚少。突触或二尖瓣与 GC 的分子特性以及 GC 与二尖瓣细胞的相互关系突触可能会有所不同，分析将解决这个基本问题并提供合理的结果。气味处理功能分析的解释的基础此外，我们将解决。突触并置沿 2o 树突的空间分布以及特征的程度因为我们要解决的问题是：对整个神经系统都很重要，我们预计结果将对了解整个大脑神经元的靶向性、层流特异性和突触连接性。