PHYSIOLOGY OF THE DEVELOPING OLFACTORY EPITHELIUM

描述：（改编自申请人的摘要）嗅觉提供 关键信息给年轻人。嗅觉线索引导新生儿 喂养并允许兄弟姐妹从其他同种中被识别出来。 母亲或环境线索的印记发生在生命早期， 嗅觉系统正在迅速发展。无数的，解剖学上的， 免疫细胞化学和分子遗传学研究已经取得进展 了解早期发育过程中发生的变化。 使用活性依赖性标记的生理学研究已经证明， 嗅球和高级嗅觉中心在 偏好学习和印记。然而，几乎没有任何信息 关于嗅觉上皮的基本生理发育，或者 在偏好学习或印记过程中可能发生的变化。我们 建议功能性地描述发育中的嗅上皮 使用常规的电生理和钙离子 成像方法和一种新的活性依赖性免疫标记技术。 之所以选择这种新兴的发展模式，是因为它孕育了一年- 圆形，受精和发育在外部迅速发生， 可以维持大量的时间分期的胚胎。我们的首要目标是 以确定何时施肥后的电压，钙和第二 抑制气味结合事件所需的信使门控电流 变成动作电位发生器。我们的第二和第三个目标的特点是 气味敏感性的时间发展和空间分布 气味刺激的嗅觉受体神经元（ORN）。气味刺激的ORN 将用离子通道渗透探针1-氨基-4- 胍基丁烷（AGB）和抗AGB IgG抗体。互补 电生理和钙成像研究将表征 原位和单独开发ORN的响应特性。最终 目的是确定气味环境在功能性 嗅上皮的发育。建议的研究将有助于 确定在职能发展的关键时期， 嗅觉上皮，并可能提供洞察的相对作用， 正常发育过程中的环境与程序化遗传事件 流程.

DESCRIPTION: (Adapted From the Applicant's Abstract) Olfaction provides critical information to the very young. Olfactory cues guide neonates to feed and permit siblings to be recognized from other conspecifics. Imprinting on maternal or environmental cues occurs early in life when the olfactory system is rapidly developing. Numerous, anatomical, immunocytochemical and molecular genetic studies have advanced out understanding of the changes occurring during early development. Physiological studies, using activity dependent markers, have demonstrated the essential roles of the olfactory bulb and higher olfactory centers in preference learning and imprinting. There is, however, little information about the basic physiological development of the olfactory epithelium or the changes that might occur during preference learning or imprinting. We propose to functionally characterize the developing olfactory epithelium of the zebrafish using conventional electrophysiological and calcium imaging methods and a novel activity-dependent immunolabeling technique. This emerging developmental model was selected because it breeds year- round, fertilization and development occur externally and rapidly and large numbers of time-staged embryos can be maintained. Our first aim is to determine when after fertilization the voltage, calcium and second messenger-gated currents required to transduce an odorant-binding event into an action potential develop. Our second and third aims characterize the temporal development of odor sensitivity and the spatial distribution of odor-stimulated olfactory receptor neurons (ORNs). Odor-stimulated ORNs will be labeled with an ion channel permeant probe, 1-amino-4- guanidobutane (AGB), and anti-AGB IgG antibodies. Complementary electrophysiological and calcium imaging studied will characterize the response properties of developing ORNs in situ and individually. The final aim is to determine the role odor environment play in the functional development of the olfactory epithelium. The studies proposed will help identify the critical periods in the functional development of the olfactory epithelium and may provide insight into the relative roles of environment versus programmed genetic events in normal developmental processes.