Development of olfactory glomeruli

描述（由申请人提供）：嗅觉信息的编码始于动物检测和区分气味的能力。在小鼠嗅觉系统中，这是由大约1000个功能性气味受体基因家族完成的，每个基因在数千个神经元中表达。成熟的嗅觉神经元只表达来自1个等位基因的1个气味受体基因。气味受体（OR）对于数千个相同的轴突汇聚到嗅球上对称分布的2个肾小球，从而产生大约2000个肾小球至关重要。小鼠遗传学和神经发育的结合使得对这些过程的分子解剖成为可能。这个项目继续分析老鼠的嗅觉系统。在Aim 1中，将确定2个高度相关的ORs的时间发育，它们对应于嗅球表面上空间相关的位置。这一分析将确定肾小球形成的开始是否与其在嗅球上的最终位置相关。一项平行的研究将确定改变给定轴突群的轴突数量是否会影响其收敛位置。在Aim 2中，多态OR蛋白将探测OR中的结构域是否对汇聚到肾小球的轴突具有特异性。这些实验将为嗅觉肾小球的发育提供基础。所产生的结果将详细说明嗅球上是否存在由梯度确定的固有位置，以及嗅觉系统中是否存在未被充分认识的可塑性。嗅觉感觉神经元不断重建与嗅球连接的代码的过程，可能会让我们对大脑其他区域的轴突寻路有所了解。

DESCRIPTION (provided by applicant): The coding of olfactory information begins with an animal's ability to detect and discriminate odorants. In the mouse olfactory system this is accomplished by a family ofapproximately 1000 functional odorant receptor genes each of which is expressed in thousands of neurons. A mature olfactory neuron expresses only 1 odorant receptor gene from only 1 allele. Odorant receptors (OR) are critical for the convergence of thousands of identical axons into 2 symmetrically located glomeruli on an olfactory bulb thereby creating approximately 2000 glomeruli. The marriage of mouse genetics and neural development has allowed for molecular dissection of these processes. This project continues with the analysis of the mouse olfactory system. In Aim 1, the temporal development will be determined for 2 highly related ORs that correspond to spatially related positions on the surface of the olfactory bulb. This analysis will determine if the onset of glomerular formation correlates with its final position on the olfactory bulb. A parallel study will determine if altering the number of axons for a given axonal population affects its position of convergence. In Aim 2, polymorphic OR proteins will probe if domains in the OR impart specificity to axons that converge into glomeruli. These experiments will provide a foundation for how olfactory glomeruli develop. Results generated will elaborate whether there are intrinsic positions on the olfactory bulb that are laid down by gradients and if there is an under appreciated plasticity in the olfactory system. The process by which olfactory sensory neurons are constantly re-establishing codes of connectivity to the olfactory bulb, may give insights into axonal pathfinding in other regions of the brain.