OLFACTORY MIXTURE INTERACTIONS--MECHANISMS AND EFFECTS

这项提议的广泛目标是了解分子、细胞、 和系统级别的机制负责转导、检测、 以及气味混合物及其成分的识别。这包括 了解(I)混合物相互作用的机理和 嗅觉传导和(Ii)混合物相互作用的影响 神经编码和行为辨别对刺激质量的影响 强度。我们将使用带刺龙虾(Panulirus Argus)作为 实验动物系统，并将刺激物设置为7种气味 化合物--AMP、甜菜碱、半胱氨酸、谷氨酸、琥珀酸、牛磺酸和 铵--已经定义了二元混合物的相互作用 来自行为和细胞外电生理学的研究 嗅觉受体细胞。具体目标如下：(一) 考察竞争性和非竞争性抑制结合的作用 嗅觉感受器细胞上结合部位的气味化合物之间 在膜中产生混合物的相互作用，使用生化 技巧。这些结合部位在嗅觉器官中的位置 也将使用透射电子显微镜进行测定。(Ii) 确定上述混合物相互作用的电学基础 7个化合物，利用全细胞膜片钳技术研究(A) 单一复合气味物质的兴奋和抑制反应及其作用 二元混合物和(B)这些反应的离子依赖性。这 研究的重要意义在于，它和其他工作将产生 同样的物种和相同的化学物质，对嗅觉的理解 事件--从受体与气味的结合到离子的产生 受体细胞中的电导、受体电位和动作电位， 到行为--支配转导、检测、感知和 气味混合物的鉴别。

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.