Functional Recovery of Sensory Input to Olfactory Bulb

拟议中的实验使用小鼠嗅觉系统作为模型，以了解神经元如何恢复 在大量神经元损失后，与中枢神经系统中的靶点的功能连接， 后续再生。哺乳动物的嗅觉系统具有惊人的再生能力 以及其初级感觉神经元（嗅觉感觉神经元）在甚至完全丧失之后的再生。 然而，感觉神经元轴突向其在大脑中的适当靶点-肾小球的再生长， 嗅球-似乎是不完美的，有许多轴突接触不适当的肾小球。的 拟议中的实验将第一次探讨这种错误的定位是如何改变肾小球活动图的 通常代表气味信息。嗅觉感觉神经元的基因编码指示物 激活将用于比较正常和上皮损伤恢复小鼠中的气味呈现。 与此同时，对单一分子鉴定受体类型的重靶向的组织学分析将允许 对这一现象进行了详细的解剖分析提出了实验，其中a）调查 肾小球活动图再生的时间过程以及它们在 B）测试感觉神经元重定向的精确度是否取决于气味诱发的 神经元;和c）研究嗅觉神经元的气味反应特性之间的关系。 感觉神经元及其对肾小球靶点的选择实验应该产生第一个通用的 损伤和恢复后气味功能表征改变程度的图片，以及 指出嗅觉神经元和它们的目标之间的连接被改造的机制。 肾小球神经再支配的错误可能是人类嗅觉功能障碍的潜在机制 由于创伤或感染而失去嗅觉的恢复中。这些实验可以提供改进的 细胞水平的解释，这种临床缺陷，并可能建议治疗策略。更 一般来说，重建适当的神经连接是完全恢复功能的先决条件。 任何感觉或运动系统。例如，在恢复外围设备后，与CMS的连接不正确 神经纤维可引起痛觉过敏和其它神经病。这项工作可能会让我们深入了解 这些和其他与不适当的神经元连接有关的综合征的治疗策略。

The proposed experiments use the mouse olfactory system as a model to understand how neurons restore functional connections to their targets in the central nervous system after massive neuronal loss and subsequent regeneration. The mammalian olfactory system has the remarkable capacity for regeneration and regrowth of its primary sensory neurons (olfactory sensory neurons) after even a complete loss. However, the regrowth of sensory neuron axons to their appropriate targets in the brain - the glomeruli of the olfactory bulb - appears to be imperfect, with many axons contacting inappropriate glomeruli. The proposed experiments will, for the first time, ask how this mistargeting alters the glomerular maps of activity that normally represent odor information. A genetically-encoded indicator of olfactory sensory neuron activation will be used to compare odorant representations in normal and epithelial lesion-recovered mice. In parallel, histological analysis of the retargeting of a single, molecularly-identified receptor type will permit a detailed anatomical analysis of this phenomenon. Experiments are proposed which a) investigate the time-course of regeneration of glomerular activity maps and the precision with which they recover after lesion; b) test whether the precision of sensory neuron retargeting depends on odorant-evoked activation of the neurons; and c) investigate the relationship between the odorant response properties of olfactory sensory neurons and their choice of glomerular target. The experiments should generate the first general picture of the extent to which functional representations of odors are altered after lesion and recovery, and point to mechanisms by which connections between olfactory neurons and their targets are reformed. Errors in the reinnervation of glomeruli are likely mechanisms underlying olfactory dysfunction in humans recovering from olfactory loss due to trauma or infection. These experiments may provide improved cellular-level explanations for such clinical deficits and could suggest therapeutic strategies. More generally, reestablishing appropriate neural connectivity is a prerequisite for the full recovery of function of any sensory or motor system. For example, incorrect connections to the CMSafter recovery of peripheral nerve fibers can cause hyperalgesia and other neuropathies. This work could potentially yield insight into treatment strategies for these and other syndromes related to inappropriate neuronal connections.