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，以了解神经元是如何恢复的 在大量神经元丢失后，与其在中枢神经系统中的靶的功能连接 随后的再生。哺乳动物的嗅觉系统具有惊人的再生能力 甚至在完全丧失后，其初级感觉神经元(嗅觉感觉神经元)也会重新生长。 然而，感觉神经元轴突的再生到它们在大脑中的适当靶点-- 嗅球似乎并不完美，许多轴突接触到不适当的肾小球。这个 拟议中的实验将首次提出这种错误定位如何改变肾小球活动地图的问题。 它们通常代表气味信息。嗅觉感觉神经元的遗传编码指标 激活将用于比较正常小鼠和上皮损伤恢复小鼠的气味表现。 同时，对单一的、分子识别的受体类型的重定向的组织分析将允许 对这一现象进行了详细的解剖分析。提出了实验方案，a)研究了 肾小球活动图再生的时间进程及其恢复的精度 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激活 以及c)研究嗅觉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 损伤和恢复后气味的功能表征改变的程度的图片，以及 指出嗅觉神经元和它们的靶点之间的连接被重塑的机制。 肾小球再神经支配的错误可能是人类嗅觉功能障碍的机制 从创伤或感染导致的嗅觉丧失中恢复的。这些实验可能会提供更好的 对这种临床缺陷的细胞水平的解释，并可能提出治疗策略。更多 一般来说，重建适当的神经连接是完全恢复神经功能的先决条件 任何感觉或运动系统。例如，外围设备恢复后与CMS的连接不正确 神经纤维可以引起痛觉过敏和其他神经疾病。这项工作可能会对 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.