Dynamic Aspects of Olfactory Signal Transduction

嗅觉信号转导的动态方面

• 批准号: 8620640
• 负责人: JOHANNES REISERT
• 金额: $ 29.85万
• 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 2016-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8620640
• 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.

描述(申请人提供)：动物生活在一个不断变化和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感受器神经元(ON)。兽类识别气味，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--嗅球。这是通过激活气味受体，通过G蛋白偶联级联导致cAMP产生，并打开存在于嗅觉纤毛上的离子通道并随后去极化实现的。气味特异性是通过在小鼠和人类的约1000个不同受体中只有一种类型的气味受体在给定的ORN中表达来提供的。嗅觉信号转导的大多数主要成分已经被识别出来。我们的目标是确定什么限制和控制嗅觉传导成分相互作用的动力学，这是如何控制动作电位的产生和编码的，以及行为方面的影响，特别是气味识别和嗅觉的启动。利用电生理技术，我们将研究小鼠Orns是如何传递气味刺激的。通过使用快速、重复的刺激来模拟高频、嗅觉驱动的气味传递，我们将确定On是仅仅报告气味浓度的快速变化，还是实际上它们自己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在嗅觉传导动力学中的功能作用(自1972年发现以来，其功能一直没有被发现)，以及不同的气味受体在塑造气味诱导反应的时间过程中的作用。快速和精确的嗅觉传导的重要性将通过对转基因小鼠的行为测试来研究，以调查气味识别的速度和准确性之间的权衡。在主动嗅觉探查期间监测呼吸频率将使我们能够确定ORN动力学和外周对中枢的影响在控制呼吸和嗅探率变化方面的贡献。