OLFACTORY GLOMERULI--CELLULAR AND NETWORK MECHANISMS

描述：(摘自摘要)因其特有的解剖学特征 长期以来，人们一直怀疑肾小球是 功能相关的嗅觉感受器神经元(ONs)的收敛。 这得到了经典的2-DG实验的支持，实验表明不同的 气味会激活不同的肾小球。然而，隐晦的本质是 嗅觉接收-转导使我们很难超越这一点 相对笼统的概念。生物物理学和分子生物学研究进展 嗅觉转导和发现一个大的、多基因家族 推测的嗅觉受体基因(Orgs)已经彻底改变了我们的思维。 关于嗅觉接收。哺乳动物的嗅觉上皮由 在四个解剖上不同的区域中，Orns仅在其中表达器官 多基因家族的四个亚群之一。在这些“表达式”中 区域“表达相同器官的单个兽人是随机分散的。 然而，最近的发现表明，来自Orns的轴突表达相同的 Org在到达鳞茎的途中会聚，并终止于相同的几个肾小球。 这意味着肾小球是Orns的汇合点，它“看到” 气味分子上也存在相同的分子亚域。在某种程度上， 这是正确的，这就是说，提取关于 特定的气味分子是神经计算的结果。首字母 这一计算阶段发生在肾小球。ONS将信息传输到 大脑的其余部分通过二尖瓣/簇状细胞，输出神经元 灯泡。这种转移最初是由神经元间网络 肾小球。这项研究的主要前提是几乎什么都没有 已知肾小球的功能组织。古典主义 解剖学研究提供了一些关于突触的信息 组织，但对其功能特征知之甚少 不同类型的肾小球旁(JG)神经细胞的药理学 肾小球突触，或肾小球内的动力学和可塑性 突触处理。肾小球间的相互作用长期以来一直被怀疑， 目前的肾小球概念在理论上是隐含的 但缺乏对肾小球相互作用的严谨分析。 肾小球研究的主要障碍是JG细胞太小， 这使得经典生理学几乎无法接触到它们 接近了。为了克服这一障碍，PI开发了第一个 哺乳动物嗅球切片的制备。这种制剂是 生理强健，并提供功能完好的通道 肾小球的微回路。少年派已经获得了一部小说 关于不同功能的JG细胞类型和突触可塑性的见解 (LTP)。拟议研究的目标是使用细胞外和细胞内 以及全细胞穿孔贴片记录方法和细胞内标记 研究肾小球的膜、突触和网络机制 相邻肾小球之间的加工和功能相互作用。

Description: (from the abstract) Because of their characteristic anatomical organization, it has long been suspected that glomeruli are sites of convergence for functionally related olfactory receptor neurons (ORNs). This was supported by classical 2-DG experiments showing that different odors activate different glomeruli. However, the obscure nature of olfactory reception-transduction made it difficult to move beyond this relatively general notion. Progress in the biophysics and molecular biology of olfactory transduction and the discovery of a large, multigene family of putative olfactory receptor genes (ORGs) have revolutionized our thinking about olfactory reception. The mammalian olfactory epithelium is composed of four anatomically distinct zones within which ORNs express ORGs from only one of four subgroups of the multigene family. Within these "expression zones" individual ORNs that express the same ORGs are randomly dispersed. However, recent findings suggest that axons from ORNs expressing the same ORG converge en route to the bulb and terminate in the same few glomeruli. This implies that glomeruli are sites of convergence for ORNs that "see" the same molecular sub-domains present on odor molecules. To the extent that this is correct, it follows that the extraction of information about specific odor molecules is the result of neural computation. The initial stage of this computation occurs in glomeruli. ORNs transfer information to the rest of the brain via mitral/tufted cells, the output neurons of the bulb. This transfer is initially regulated by the interneuronal network of the glomerulus. The major premise of this research is that almost nothing is known about the functional organization of glomeruli. Classical anatomical studies have provided some information about the synaptic organization, but very little is known about the functional characteristics of distinct juxtaglomerular (JG) interneuronal cell types, the pharmacology of glomerular synapses, or the dynamics and plasticity of intraglomerular synaptic processing. Interglomerular interactions have long seen suspected, and are theoretically implied by current notions of ORN-glomerular convergence, but rigorous analyses of glomerular interactions are lacking. The major impediment to research on glomeruli is the small size of JG cells, which has rendered them virtually inaccessible to classical physiological approaches. To overcome this obstacle the PI has developed the first mammalian olfactory bulb slice preparation. This preparation is physiologically robust and provides access to the functionally intact microcircuitry of the glomerulus. The PI has already obtained novel insights about functionally distinct JG cell types and synaptic plasticity (LTP). The goal of the proposed research is to use extra- and intracellular and whole-cell perforated-patch recording methods and intracellular labeling to characterize membrane, synaptic, and network mechanisms of glomerular processing and functional interactions among neighboring glomeruli.