DEVELOPMENT OF SEXUALLY DIMORPHIC OLFACTORY GLOMERULI

性二态性嗅球的发育

• 批准号: 6219169
• 负责人: JOHN G HILDEBRAND
• 金额: $ 2.33万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6219169
• 关键词: Manduca; central neural pathway /tract; developmental neurobiology; experimental brain lesion; gender difference; glia; histogenesis; histology; hormone regulation /control mechanism; intercellular connection; neural information processing; neural plasticity; neuroendocrine system; neurogenesis; olfactory lobe; pheromone; sensory receptors; sensory signal detection; tissue /cell culture

An important challenge in developmental neurobiology is to unravel mechanisms responsible for the influences exerted by afferent innervation on the development of its targets. Good examples of such phenomena are found in the olfactory system. In the brains of all species studied to date, development of the primary olfactory center with its characteristic array of synaptic glomeruli depends dramatically on innervation by primary- afferent axons of olfactory receptor cells. How sensory axons control the formation of glomeruli, and how odotopy -- the orderly spatial representation of attributes of odor molecules -- arises in the glomerular array, are pressing problems. This project will focus on the development of individual glomeruli and their uniglomerular projection neurons, endowed with characteristic "molecular receptive range" properties and will take advantage of a remarkable model system, the sexually dimorphic olfactors lobe in the brain of Manduca sexta. In particular, we will investigate the postembryonic development of the prominent macroglomerular complex in the male's olfactory lobes. This unique complex receives primary-afferent inputs solely from male-specific olfactory receptor cells, which induce the formation of the macroglomerular complex and are specialized to detect individual components of the female's sex-pheromone blend. The complex comprises two glomerular substructures, each of which receives and processes primary-afferent input about a different one of the two key components of the blend. These identified, odotopically defined glomeruli also contain neurites of male-specific central neurons, most notably uniglomerular projection neurons, which participate in specialized synaptic circuitry for processing sensory input about pheromone. As specific aims, the proposed studies ask: (1) how the macroglomerular complex develops, (2) what role(s) glial cells play in its development, (30 whether there are quantitative and temporal requirements for male-afferent control of its development, and (4) whether male-specific sensory axons have molecular specializations that might be responsible for induction of the macroglomerular complex. The ultimate goals of the line of research represented by this proposal are; (a) to ascertain the cellular and molecular mechanisms underlying the decisive role of sensory axons in the development of glomeruli, (b) to discover how primary-afferent and central elements ultimately destined to have similar, distinctive molecular receptive ranges come to associate with each other, and (c) to determine whether glial cells participate in the development of all of the glomeruli in a particular species. This is the first effort, in any species, to ascertain developmental processes and mechanisms underlying morphogenesis of anatomically identified olfactory glomeruli with known functional specificity. This research promises to add significantly to understanding of cell-cell interactions in the development of functionally specialized, modular neuropil in the central nervous system and thus to fuel progress toward improved understanding and treatment of developmental disorders of sensory systems.

发育神经生物学的一个重要挑战是 负责传入神经支配影响的机制 发展其目标。 这种现象的好例子是 在嗅觉系统中发现。 在所有被研究的物种的大脑中， 初级嗅觉中枢的发育及其特点 突触小球的排列显著依赖于初级神经支配， 嗅觉感受器细胞的传入轴突。 感觉轴突如何控制 肾小球的形成，以及如何odotopy-有序的空间 代表气味分子的属性--出现在肾小球 阵列，是紧迫的问题。 本项目将侧重于个体肾小球的发育， 它们的单肾小球投射神经元，具有 “分子接受范围”的性质，并将利用一个 一个值得注意的模型系统，大脑中的两性嗅觉叶 曼陀卡六。 特别是，我们将研究胚胎后 在男性的突出的大肾小球复合体的发展 嗅叶 这个独特的复合体接受初级传入输入 仅来自雄性特异性嗅觉受体细胞，其诱导 巨球复合体的形成，并专门检测 雌性的性信息素混合物 复杂 包括两个肾小球亚结构，每个亚结构接收并 处理关于两个键中不同键的初级传入输入 混合物的成分。 这些确定的，odotopically定义的肾小球 还含有男性特有的中枢神经元的神经突，最值得注意的是 单肾小球投射神经元，参与专门的突触 用于处理关于信息素的感觉输入的电路。 作为具体的目标，拟议的研究问：（1）如何大肾小球 复杂的发展，（2）什么作用（S）胶质细胞在其发展中发挥作用，（30 是否有数量和时间的要求，男性传入 控制其发展，和（4）是否男性特有的感觉轴突 有分子特化，可能负责诱导 巨球复合体 研究路线的最终目标 该提案的代表是：（a）确定蜂窝和 感觉轴突在神经系统中起决定性作用的分子机制 肾小球的发育，（B）以发现初级传入和中枢 元素最终注定有相似的，独特的分子 接受范围来相互关联，（c）确定 胶质细胞是否参与了所有肾小球的发育 在一个特定的物种。 这是第一次努力，在任何物种，以确定发展 解剖学形态发生的过程和机制 鉴定出具有已知功能特异性的嗅球。 这 研究有望大大增加对细胞-细胞的理解 在发展功能专门化、模块化 中枢神经系统中的神经递质，从而推动向 提高对感觉发育障碍的认识和治疗 系统.