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，这为气味分子与嗅觉感受器细胞表面的最初相互作用提供了一个微环境。这种粘液在决定刺激物的溶解性和扩散性方面很重要，可以改变嗅觉感受器神经元对气味的反应。粘液是由副腺分泌的，而不是由受体本身分泌的，其组成是可变的；它是嗅觉功能的受体周围调节器。调节粘液分泌和组成的神经机制可能会反过来受到气味刺激的影响。要充分了解嗅觉感受器的功能，必须了解这些特性和机制。这个项目将对嗅觉粘膜进行实验操作，并使用免疫组织化学和药理学来探索气味和分泌物之间的关系。确定通向粘膜的神经通路将与确定参与分泌调节的神经递质的特征相结合。香味剂和药物剂将被测试其刺激神经调节剂释放和激活分泌的能力。分泌产物中的功能性碳水化合物将被鉴定，分泌细胞内的蛋白质也将被鉴定，以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处理感觉输入的调节这一重要主题，结果将对我们如何看待嗅觉系统以及其他感觉感受器的总体调节具有重要意义。

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.