OLFACTORY FUNCTION FOLLOWING PERIPHERAL AND CENTRAL LESION

周围和中枢病变后的嗅觉功能

• 批准号: 6104312
• 负责人: STEVEN L. YOUNGENTOB
• 金额: $ 12.54万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6104312
• 关键词: anosmia; behavior test; brain electrical activity; conditioning; experimental brain lesion; immunocytochemistry; laboratory rat; mucosa; nervous system regeneration; neural information processing; odors; olfactions; olfactory disorder; olfactory lobe; olfactory stimulus; psychophysics; respiratory epithelium; sensory discrimination

A limitation in the capacity of the peripheral olfactory system to reconstitute completely or reconnect correctly following insult could determine the degree of dysfunction and whether it persists. Previously, we used an interdisciplinary approach to document a capacity for recovery of the system anatomically (reconstitution of the epithelium and reinnervation of the bulb) and functionally (restoration of an odorant identification task and reestablishment of optically recorded mucosal activity patterns). However, the time course for both behavioral and electrophysiological recovery lagged that for anatomical recovery (using such measures as GAP-43 expression, OMP-expression, basal cell proliferation and re-innervation with the bulb). Although the recovered system demonstrated a capacity to support function, the question as to whether the perception of odorant quality has been changed as a function of damage and recovery still remains. Using the same interdisciplinary approach we propose to; 1) further define the relationship between time post-lesion and the preparedness of the olfactory system to support criterion level performance on an odorant identification task; 2) test the hypothesis that odor ant quality identification is preserved following reconstitution of the system; 3) determine whether and when bulbar electrophysiological activity patterns recover, and determine the correspondence between the neurophysiological recovery of the mucosa and bulb; and 4) assess, using anatomical and immunochemical techniques, metabolic activation of the bulb and expression of c-fos in response to odorants. The anatomical assessments of recovery will be related in time register to the behavioral and neurophysiological recovery process. We also propose to investigate whether and how partial destruction of either the olfactory mucosa or olfactory bulb can disrupt odorant quality coding. Clinical observations suggest that deficits can be either global or specific to a subset of odorants, in patients with peripheral or central damage. We previously observed that ethyl bromide lesioned rats, retaining as little as 5% of the normal complement of olfactory epithelium, functioned at a hyposmic level on an odorant identification task. More importantly, one of two condition of hyposmia did exist, namely, a deficit in performance across all odorants of the identification task or a deficit restricted to some subset. These clinical and experimental observations raise the question as to how much epithelium is required to support normal function, and is there a relationship between the area damaged and the odorants on which performance is lost. We propose to examine whether and to what degree the pattern of behavioral deficit on an odorant identification task is related to the extent and pattern of epithelial destruction. Similarly, using 2-DG patterns of activation as our guide, we will examine the degree to which focally restricted lesions of the olfactory bulb will result in selective odorant identification deficits. These studies will refine our understanding of the capacity of the olfactory system to recover following peripheral lesions. Further, they will provide insights into the importance of spatial activation at the level of the olfactory mucosa and bulb. As a result, we will better understand the relationship between damage to these structures and the functional manifestation.

外围嗅觉系统能力的限制 侮辱后完全重建或正确重新连接可能 确定功能障碍的程度及其是否持续存在。 之前， 我们使用跨学科的方法来记录恢复能力 系统的解剖学（上皮的重建和 灯泡的神经支配）和功能上（气味物质的恢复） 光学记录粘膜的识别任务和重建 活动模式）。 然而，行为和行为的时间进程 电生理恢复落后于解剖恢复（使用 GAP-43 表达、OMP 表达、基底细胞等指标 增殖和球茎的重新神经支配）。 虽然已经康复 系统表现出支持功能的能力，问题是 对气味质量的感知是否随着以下因素而改变 损害和恢复仍然存在。 使用相同的跨学科 我们建议的方法； 1）进一步定义时间之间的关系 病变后和嗅觉系统的准备支持 气味识别任务的标准水平表现； 2）测试 假设气味蚂蚁质量识别在以下情况下得以保留 重建系统； 3) 判断是否以及何时延髓 电生理活动模式恢复，并确定 粘膜的神经生理恢复与 电灯泡; 4) 使用解剖学和免疫化学技术进行评估， 球茎的代谢激活和 c-fos 的表达响应 气味剂。 恢复的解剖学评估将及时相关 记录行为和神经生理恢复过程。 我们 还建议调查是否以及如何部分销毁 嗅粘膜或嗅球可以破坏气味质量编码。 临床观察表明，缺陷可能是全局性的，也可能是 特定于外周或中枢患者的气味剂子集 损害。 我们之前观察到溴乙烷损伤大鼠，保留 少至嗅觉上皮正常补体的 5%， 在气味识别任务中在低嗅觉水平下发挥作用。 更多的 重要的是，确实存在嗅觉减退的两种情况之一，即缺乏 识别任务中所有气味剂的表现或缺陷 仅限于某些子集。 这些临床和实验观察 提出一个问题：需要多少上皮来支持正常的 功能，损坏面积与损坏面积之间是否存在关系？ 失去性能的气味剂。 我们建议审查是否以及 对气味剂的行为缺陷模式到什么程度 识别任务与上皮细胞的范围和模式有关 破坏。 类似地，使用 2-DG 激活模式作为我们的指导，我们 将检查局灶性限制性病变的程度 嗅球会导致选择性气味识别缺陷。 这些研究将加深我们对 嗅觉系统在周围病变后恢复。 此外，他们 将深入了解空间激活的重要性 嗅粘膜和嗅球的水平。 如此一来，我们就能更好地 了解这些结构的损坏与 功能表现。