MECHANISMS OF OLFACTORY RECEPTOR NEURON ADAPTATION

嗅觉受体神经元适应机制

• 批准号: 2126493
• 负责人: William Craig Michel
• 金额: $ 8.74万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-01-01 至 1996-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2126493
• 关键词: Malacostraca; action potentials; alternatives to animals in research; biological signal transduction; chemoreceptors; dendrites; electrical conductance; electrical potential; electrophysiology; environmental adaptation; membrane channels; membrane potentials; membrane transport proteins; neural conduction; neural information processing; neural inhibition; neural plasticity; olfactions; olfactory stimulus; olfactory threshold; phosphorylation; receptor sensitivity; response generalization; sensory mechanism; stimulus /response; tissue /cell culture; voltage /patch clamp

Sensory receptors are able to detect and discriminate relevant stimuli from backgrounds that vary in stimulus quality and quantity. Studies of these events revealed that sensory adaptation is as fundamentally important to receptor cell output as activation. Indeed, the progression from stimulus reception to termination of receptor cell response is governed by the kinetics of transduction (activation) and adaptation (inactivation). In recent years, investigations utilizing contemporary path clamp electrophysiological and biochemical techniques have substantially advanced our understanding of the mechanisms of olfactory receptor cell activation but the mechanisms of inactivation are largely unknown. The proposed research will utilize these proven techniques to critically examine the mechanisms of olfactory adaptation. In other sensory systems, voltage and Ca+2-activated conductances, electrogenic pump activity, receptor desensitization and changes in ion composition, have been implicated in adaptation. Two types of adaptation, one the result of changes in the background odor environment (background adaptation), the other the previous response history of an cell (receptor cell fatigue), are proposed to influence the cell's current potential to respond. Background adaptation is proposed to act with slower kinetics on odor-activated conductances. Receptor cell fatigue is proposed to act with faster kinetics on the somatic voltage and Ca+2-activated conductances encoding the action potentials. The proposed research will examine the involvement of odor, voltage and Ca+2-activated conductances, as well as, electrogenic pump activity and receptor desensitization, in adaptation. Because adaptation occurs in the olfactory receptor cell, tissue which is exposed to the external environment, the cellular mechanisms of adaptation may be particularly vulnerable to the effects of toxic substances and infection. Indeed, olfactory deficits are correlated with several neurological disorders (Doty et al., 1988). Consequently, knowledge of the cellular machinery of adaptation pathways may aid in elucidating the etiologies of not only olfactory, but possibly other neurological disorders.

感觉受体能够检测并区分相关刺激 刺激质量和数量各不相同的背景。 这些研究 事件显示，感官适应对 受体细胞输出作为激活。 确实，刺激的进展 接受受体细胞反应终止的接收由 转导动力学（激活）和适应性（灭活）。 在 近年来，利用当代路径夹的调查 电生理和生化技术具有基本先进的 我们对嗅觉受体细胞激活机制的理解 但是失活的机制在很大程度上是未知的。 提议 研究将利用这些经过验证的技术来批判性地检查 嗅觉适应的机制。 在其他感觉系统中，电压和 Ca+2个激活电导，电泵活性，受体 脱敏和离子组成的变化已与 适应。 适应的两种类型，这是变化的结果 背景气味环境（背景调整），另一个 提出了细胞（受体细胞疲劳）的响应史 影响细胞当前响应的潜力。 背景适应 提出在气味激活的电导率上以较慢的动力学作用。 提议受体细胞疲劳以更快的动力学作用 躯体电压和CA+2个激活的电导 潜力。 拟议的研究将研究气味的参与， 电压和Ca+2个激活的电导以及电源泵 活性和受体脱敏，适应。 因为适应 发生在嗅觉受体细胞中，暴露于 外部环境，适应的细胞机制可能是 特别容易受到有毒物质和感染的影响。 实际上，嗅觉缺陷与几个神经系统相关 疾病（Doty等，1988）。 因此，对细胞的了解 适应途径的机械可能有助于阐明 不仅嗅觉，而且可能是其他神经系统疾病。