Perireceptor Modulation in the Olfactory Mucosa

进入脊椎动物鼻子的气味被困在一层嗅觉粘液中，这为气味分子和嗅觉受体细胞表面之间的初始相互作用提供了一个微环境。这种粘液在决定刺激的溶解度和扩散性方面很重要，并且可以改变嗅觉受体神经元对气味的反应。粘液是由副腺体而不是受体本身分泌的，其成分是可变的；它是嗅觉功能的周围感受器调节剂。调节粘液分泌和组成的神经机制可能反过来受到气味刺激的影响。为了充分了解嗅觉受体的功能，必须了解这些特性和机制。本项目将对嗅觉粘膜进行实验操作，并利用免疫组织化学和药理学方法探讨气味剂与分泌物之间的关系。粘膜神经支配通路的鉴定将与参与分泌调节的神经递质的表征相结合。将测试气味剂和药理学剂刺激神经调节剂释放和激活分泌的能力。将在分泌产物中鉴定功能性碳水化合物，也将鉴定分泌细胞内的蛋白质，以便与其他粘液分泌系统中的蛋白质进行比较。这个项目涉及到一种独特的方法来调节感觉输入的重要主题，其结果将对我们如何思考嗅觉系统和其他感觉受体的调节非常重要。

Odors coming to the nose of vertebrates are trapped in a film of olfactory mucus, which provides a microenvironment for the initial interactions between odorant molecules and the olfactory receptor cell surfaces. This mucus is important in determining the solubility and diffusibility of the stimuli, and can change the response of olfactory receptor neurons to odorants. The mucus is secreted by accessory glands rather than the receptors themselves and its composition is variable; it is a perireceptor modulator of olfactory function. Neural mechanisms that regulate the secretion and composition of the mucus may in turn be influenced by odorant stimuli. To fully understand olfactory receptor function, these properties and mechanisms must be known. This project will experimentally manipulate the olfactory mucosa, and use immunohistochemistry and pharmacology to explore the relations between odorants and secretions. Identification of the innervating pathways to the mucosa will be combined with characterization of the neurotransmitters involved in regulation of secretion. Odorants and pharmacological agents will be tested for their ability to stimulate neuromodulator release and activate secretion. Functional carbohydrate compounds will be identified in the secretory products, and proteins within the secretory cells will also be identified to compare with those found in other mucus-secreting systems. This project involves a unique approach to the important topic of modulation of sensory input, and results will be important to how we think about olfactory systems, and modulation of other sensory receptors in general.