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 侮辱后完全重新构建或正确重新连接 确定功能障碍的程度及其是否持续。 之前， 我们使用跨学科的方法来记录恢复能力 该系统的解剖学（上皮的重构 重新支配灯泡）和功能（恢复气味剂 识别任务和重新建立光学记录的粘膜 活动模式）。 但是，行为和行为的时间课程 电生理恢复滞后于解剖学恢复（使用 诸如GAP-43表达，OMP表达，基础细胞等措施 与灯泡的增殖和重新启动。 虽然恢复了 系统证明了支持功能的能力，关于 是否随着气味质量的看法已随着 损坏和恢复仍然存在。 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 尸体后和嗅觉系统的准备 气味识别任务上的标准级别的性能； 2）测试 假设有气味蚂蚁质量识别遵循 重建系统； 3）确定是否以及何时灯泡 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评估 灯泡的代谢激活和C-FOS的表达响应于 气味。 恢复的解剖学评估将随着时间的及时关联 注册到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破坏任何一个 嗅觉粘膜或嗅球会破坏气味质量编码。 临床观察结果表明，赤字可以是全球或 特定于一部分气味剂，外围或中央患者 损害。 我们先前观察到溴化乙基病变的大鼠保留 少于嗅觉上皮的正常补体的5％， 在低气味识别任务下在低症状水平上发挥作用。 更多的 重要的是，确实存在两种低血症状况之一，即赤字 在标识任务或赤字的所有气味中的性能 仅限于某个子集。 这些临床和实验观察结果 提出有关支持正常需要多少上皮的问题 功能，并且该区域受损与该区域之间存在关系 性能丢失的气味。 我们建议检查是否以及 在多气味上的行为不足模式在多大程度上 识别任务与上皮的程度和模式有关 破坏。 同样，使用2-DG激活模式作为我们的指南，我们 将检查局部限制病变的程度 嗅球将导致选择性气味鉴定缺陷。 这些研究将完善我们对 嗅觉系统以恢复外周病变。 此外，他们 将提供有关在空间激活的重要性的见解 嗅觉粘膜和灯泡的水平。 结果，我们会更好 了解对这些结构的破坏与 功能表现。