A Multicellular Method to Study Olfactory Encoding

描述(由申请人提供)：这份建议书概述了 一种研究编码的多细胞记录方法的实现 由嗅觉感觉神经元提供的信息。关于气味的感官信息 由多个不同的嗅觉神经元同时提取并分布为 整个嗅球的肾小球的动作电位序列。这个 嗅觉神经元对气味的反应通常被描述为 兴奋性，但在对分离神经元的研究中，既有兴奋性也有抑制性 气味反应已经被报道过，同样的气味可以改变不同的 不同神经元的膜电导。这种可变性的存在具有 对这些回应是真实的还是人为的提出了质疑，它确实做到了 强调了我们对编码的基本性质的了解是多么有限 流程就是。目前的方法不太适合对气味进行严格的检查 编码。我们建议开发一种新的多细胞电记录 解决这个问题的技术该技术将允许记录气味- 同时在单细胞水平上引发电活动 嗅觉感觉神经元的数量很少。这种能力将代表着 一项技术突破，可以显著提高我们对 嗅觉神经编码。这种方法将利用孤立的嗅觉 上皮组织和一组独立的玻璃微电极， 每个记录来自暴露的嗅觉纤毛的细胞外动作电流 感觉神经元。神经元将保留在完好的组织中，不需要 降解性酶处理，从而允许记录气味反应 在近乎生理的条件下。因为它的多细胞特性 再加上长期录制的可能性，该方法提供了一种 独特的、高通量的气味反应生理学分析。应该是 是研究气味编码的基本机制的理想工具 它将为转基因研究提供一种有效的手段 制造成本很高的动物。

DESCRIPTION (provided by applicant): This proposal outlines the development and implementation of a multicellular recording method to study encoding of information by olfactory sensory neurons. Sensory information about odor is extracted by many different olfactory neurons simultaneously and distributed as trains of action potentials to glomeruli throughout the olfactory bulbs. The response of an olfactory sensory neuron to odor is usually described as excitatory, but in studies of isolated neurons, both excitatory and inhibitory odor responses have been reported, and the same odor can alter different membrane conductances in different neurons. The presence of such variability has raised questions about whether the responses are real or artifactual, and it has emphasized how limited our knowledge of the fundamental nature of the encoding process is. Present methods are not well suited for critically examining odor encoding. We propose to develop a new multicellular electrical recording technique to address the problem This technique will permit recording of odor- elicited electrical activity at the single-cell level simultaneously from a small population of olfactory sensory neurons. Such a capability would represent a technological breakthrough that could significantly advance our understanding of olfactory neural encoding. The method will utilize isolated olfactory epithelial tissue together with an array of independent glass microelectrodes, each recording extracellular action currents from the exposed cilia of olfactory sensory neurons. The neurons would remain in the intact tissue and not require degradative enzymatic treatment, thus allowing odor responses to be recorded under nearly physiological conditions. Because of its multicellular nature coupled with the possibility of long-term recordings, the method offers a unique, high-throughput physiological assay of odor responses. It should be ideal for studying the fundamental mechanisms of odor encoding with pharmacological tools, and it will offer an efficient means to study transgenic animals which are expensive to engineer.