Olfactory Bulb Local Circuits

嗅球局部电路

• 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
• 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; 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

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.

项目摘要 - 摘要 当气味配体在嗅觉上结合时，气味开始于嗅觉上皮 感觉神经元，每个神经元仅表达约1200个候选受体中的1个。轴突来自 表达相同气压受体的神经元仅收敛到2/3肾小球/嗅球 它们突触到投影神经元，每个神经元都支配了单个肾小球。深处 glomerulli，外部丛状层（EPL）内，ODO编码是由局部突触电路调节的。 与EPL的解密连接是了解中央机制的第一步 ODO处理。已经提出了EPL内部的几种本地处理的假设及其 突触组织通常被视为规范。但是，我们对 中间神经元，颗粒细胞（GC），结构，分子和地形的多样性的方式 组织会影响EPL本地电路，这是解释功能研究的障碍。我们在这里 提出有关可能影响组织的因素的一系列可检验的假设和实验 GC及其本地突触电路。这些研究以我们先前的发展和 超微结构工作以及对当前文献的系统评价和认识 已经建立了EPL组织和连通性的基本特征，但不是从经验上 测试。首先，我们建议解决克隆历史，GC的时机和顺序的假设 神经发生取决于其在嗅球中的组织/分布。使用多个 跟踪神经发生，细胞谱系/命运的策略，我们将评估GC的刺刺树状轴。 从胚胎开始，并定期延续到200天的年龄。在 补充，而不是先前的研究，我们建议仔细评估GC基本的组织 树突是传入离心调制的主要接受者（Rothermei和Rothermei和 Wachowiak，2014年； Kapoor等人，2016年； De Almeida等，2015）。其次，我们建议测试 假设EPL变化中树突状质突触的突触和分子特征 作为年龄的函数。目前，对调节树突状的结构特征知之甚少 突触或二尖瓣的分子特性如何 突触可能有所不同。分析将解决这个基本问题并提供声音 解释气味处理功能分析的基础。此外，我们将解决 突触应用沿2o树突的空间分布以及其特征的特征 突触专业随着年龄的增长而变化。因为我们建议解决的问题是 在整个神经系统中都很重要，我们预计结果将对 了解整个大脑神经元的靶向，层流特异性和突触连通性。