Dynamic Aspects of Olfactory Signal Transduction

嗅觉信号转导的动态方面

• 批准号: 8469130
• 负责人: JOHANNES REISERT
• 金额: $ 0.68万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8469130
• 关键词: A Mouse; Action Potentials; Address; Affect; Air; Animals; Behavioral; Brain; Breathing; Cell physiology; Cells; Cilia; Code; Complex; Coupled; Cyclic AMP; Detection; Discrimination; Electrophysiology (science); Environment; Family; Food; Frequencies; G Protein-Coupled Receptor Signaling; G-Protein-Coupled Receptors; GTP-Binding Proteins; Generations; Genome; Goals; Heart; Hormonal; Human; Ion Channel; Kinetics; Life; Mammals; Mate Selections; Monitor; Mus; Nasal cavity; Neurons; Noise; Odorant Receptors; Odors; Olfactory Receptor Neurons; Organism; Pattern; Peripheral; Physiology; Process; Proteins; Regulation; Reporting; Role; Sampling; Second Messenger Systems; Sensory; Shapes; Signal Transduction; Simulate; Smell Perception; Source; Specificity; Speed; Stimulus; Techniques; Time; Vertebrates; Work; base; behavior test; design; information processing; insight; knockout animal; member; mouse olfactory marker protein; olfactory bulb; olfactory marker protein; olfactory receptor; protein function; public health relevance; receptor; response; second messenger

DESCRIPTION (provided by applicant): Animals live in an environment of constantly changing and complex odorous signals, which are delivered by the inhaled air to olfactory receptor neurons (ORNs) in the nasal cavity. ORNs recognize odorants and convert odorant stimulation into action potentials to be conveyed to the first relay station in the brain, the olfactory bulb. This is achieved by activation of odorant receptors, leading to cAMP generation via a G protein-coupled cascade and the opening of ion channels present on the olfactory cilia and subsequent depolarization. Odorant specificity is provided by the expression of only one type of odorant receptor in a given ORN out of ~1000 different receptors in mice and 350 in humans. Most major components of olfactory signal transduction have been identified. Our goal is to determine what limits and controls the kinetics with which olfactory transduction components interact, how this controls action potential generation and coding and what the behavioral implications are for, in particular, odorant discrimination and initiation of sniffing. Using electrophysiological techniques, we will investigate how mouse ORNs transduce odorant stimulation. Using rapid, repetitive stimulation designed to simulate high-frequency, sniffing-driven odorant delivery, we will establish whether ORNs merely report these rapid changes in odorant concentration or if in fact they themselves actively process this information in a stimulation-frequency-dependent manner. We will determine the functional role in olfactory transduction kinetics of olfactory marker protein (the function of which has not been found since its discovery in 1972) as well as determining the role of different odorant receptors in shaping the time-course of the odorant-induced response. The importance of fast and precise olfactory transduction will be studied using behavioral testing on genetically altered mice to investigate speed-accuracy tradeoff in odorant identification. Monitoring the breathing frequency during active olfactory exploration will allow us to establish the contribution of ORN kinetics and peripheral-versus-central influence on controlling changes in breathing and sniffing rates. PUBLIC HEALTH RELEVANCE: The proposed work will address the importance of both precise timing and fast transduction of odorous signals by G protein-coupled receptors in olfactory receptor neurons from the single-cell to the complex-behavioral levels such as tracking a food source or avoiding a predator. The work has broader implications in that the results will yield fundamental insights into how members of the G protein-coupled receptor family (which comprise a large part of the genome) and neurons that express them, control time-dependent cellular processes ranging from heart beat regulation to conveying hormonal signals.

描述（由申请人提供）：动物生活在一个不断变化且复杂的气味信号的环境中，这些信号通过吸入的空气传递到鼻腔中的嗅觉受体神经元（ORN）。 ORN 识别气味并将气味刺激转化为动作电位，然后传送到大脑中的第一个中继站，即嗅球。这是通过激活气味受体来实现的，从而通过 G 蛋白偶联级联产生 cAMP，并打开嗅觉纤毛上存在的离子通道以及随后的去极化。气味特异性是通过在给定的 ORN 中仅表达一种类型的气味受体来提供的，而小鼠中大约有 1000 种不同的受体，人类中大约有 350 种不同的受体。嗅觉信号转导的大多数主要成分已被鉴定。我们的目标是确定什么限制和控制嗅觉转导成分相互作用的动力学，它如何控制动作电位的产生和编码以及行为影响是什么，特别是气味辨别和嗅觉启动。利用电生理学技术，我们将研究小鼠 ORN 如何转导气味刺激。使用旨在模拟高频、嗅探驱动的气味传递的快速、重复刺激，我们将确定 ORN 是否仅仅报告气味浓度的这些快速变化，或者实际上它们本身是否以刺激频率依赖的方式主动处理这些信息。我们将确定嗅觉标记蛋白（自 1972 年发现以来其功能尚未被发现）在嗅觉转导动力学中的功能作用，以及确定不同气味受体在形成气味诱导反应的时间过程中的作用。将通过对转基因小鼠进行行为测试来研究快速而精确的嗅觉转导的重要性，以研究气味识别中的速度与准确性权衡。在主动嗅觉探索过程中监测呼吸频率将使我们能够确定 ORN 动力学的贡献以及外周与中枢对控制呼吸和嗅觉速率变化的影响。 公共健康相关性：拟议的工作将解决嗅觉受体神经元中 G 蛋白偶联受体对气味信号的精确计时和快速转导的重要性，从单细胞到复杂的行为水平，例如跟踪食物来源或躲避捕食者。这项工作具有更广泛的意义，因为结果将产生关于 G 蛋白偶联受体家族成员（组成基因组的很大一部分）和表达它们的神经元如何控制从心跳调节到传递激素信号等时间依赖性细胞过程的基本见解。