OLFACTORY MIXTURE INTERACTIONS--MECHANISMS AND EFFECTS

这项提案的主要目标是了解分子，细胞， 以及负责转导，检测， 和气味混合物及其组分的辨别。 这包括 了解（i）混合物相互作用的机制， 嗅觉传导和（ii）混合物相互作用对 刺激质量的神经编码和行为辨别， 强度。 我们将使用多刺龙虾（Panulirus argus）作为 实验动物系统，刺激将是一组7气味 化合物- AMP、甜菜碱、半胱氨酸、谷氨酸盐、琥珀酸盐、牛磺酸和 铵--二元混合物相互作用已经定义 从行为和细胞外电生理学的研究中， 嗅觉受体细胞 具体目标如下：（一） 检查结合的竞争性和非竞争性抑制的作用 嗅觉受体细胞上结合位点的气味化合物之间 膜在混合物相互作用的产生，使用生化 技术. 嗅觉器官中这些结合位点的位置 也将使用透射电子显微镜测定。 （二） 确定涉及上述的混合物相互作用的电基础 7个化合物，使用全细胞膜片钳技术来研究（a）化合物的 对单一化合物气味剂的兴奋和抑制反应及其 二元混合物和（B）这些响应的离子依赖性。 这 研究是重要的，因为它和其他工作将产生，为 相同的物种和相同的化学物质，对嗅觉的理解 事件--从受体-气味剂结合，到产生离子 电导、受体电位和受体细胞中的动作电位， 到行为--控制着信号的传导、检测、感知， 气味混合物的辨别。

The broad objective of this proposal is to understand molecular, cellular, and systems level mechanisms responsible for the transduction, detection, and discrimination of odorant mixtures and their components. This includes gaining an understanding of (i) mechanisms of mixture interactions and olfactory transduction and (ii) the effects of mixture interactions on neural coding and behavioral discrimination of stimulus quality and intensity. We will use the spiny lobster (Panulirus argus) as the experimental animal system, and the stimuli will be a set of 7 odorant compounds -- AMP, betaine, cysteine, glutamate, succinate, taurine, and ammonium -- for which binary mixture interactions have already been defined from studies of behavior and of extracellular electrophysiology of olfactory receptor cells. The specific aims are the following: (I) Examine the role of competitive and noncompetitive inhibition of binding between odorant compounds for binding sites on olfactory receptor cell membrane in the generation of mixture interactions, using biochemical techniques. The location of these binding sites in the olfactory organ will also be determined, using transmission electron microscopy. (II) Determine the electrical basis of mixture interactions involving the above 7 compounds, using whole cell patch clamp techniques to study (a) the excitatory and inhibitory responses to single compound odorants and their binary mixtures and (b) the ionic dependence of these responses. This research is significant in that it and other work will generate, for the same species and the same set of chemicals, an understanding of olfactory events -- from receptor-odorant binding, to generation of ionic conductances, receptor potentials, and action potentials in receptor cells, to behavior -- that govern the transduction, detection, perception, and discrimination of odorant mixtures.