Trigeminal Modulation of Olfactory Responses in the Main Olfactory Epithelium

主嗅上皮嗅觉反应的三叉神经调节

• 批准号: 10063986
• 负责人: Federica Genovese
• 金额: $ 15.52万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10063986
• 关键词: Action Potentials; Address; Affect; Agonist; Area; Biosensor; Carbon Dioxide; Cations; Characteristics; Chemicals; Chemoreceptors; Detection; Electrophysiology (science); Exposure to; Fiber; Food Preferences; Free Nerve Ending; Generations; Individual; Inflammatory; Inflammatory Response; Irritants; Kinetics; Knockout Mice; Measures; Mediating; Mediator of activation protein; Methods; Migraine; Modality; Mus; Nasal cavity; Neuraxis; Neuropeptides; Nociception; Nociceptors; Nose; Odors; Olfactory Epithelium; Olfactory Pathways; Pathologic; Pathology; Perception; Peripheral; Physiologic pulse; Physiological; Physiology; Play; Population; Process; Purinoceptor; Role; Sensory; Signal Transduction; Signaling Molecule; Smell Perception; Smoking; Source; Stimulus; System; TRPV1 gene; Techniques; Testing; Trigeminal System; Variant; Wild Type Mouse; Work; base; experimental study; extracellular; neurotransmission; olfactory bulb; olfactory sensory neurons; olfactory stimulus; patch clamp; preference; receptor; response; taste system; vanillin

PROJECT SUMMARY The olfactory and trigeminal systems are usually considered independent, but most odorants activate the trigeminal system, and most irritants activate olfactory sensory neurons (OSNs). These two systems co-localize in the olfactory epithelium and bulb and in different cortical areas. Trigeminal stimulation usually reduces odor intensity perception, but it has not been established where along the olfactory pathway this inhibition takes place or which physiological mechanisms are involved. The olfactory epithelium, where the olfactory response is first generated, is a candidate locus to harbor this interaction. Here, OSNs are densely interspersed with trigeminal peptidergic fibers. These fibers can be activated by most odorants, and they can release different neuropeptides and ATP. These substances can mediate an inflammatory response, but they can also play other roles. In particular, ATP is an important extracellular signaling molecule, which is involved in neurotransmission in the peripheral and central nervous systems, as well as in the peripheral gustatory system. ATP-sensitive receptors are found in the olfactory epithelium, on both OSNs and trigeminal peptidergic fibers. However, peripheral trigeminal-olfactory interaction and the potential role of ATP as its mediator have not been studied. Using electrophysiological recordings from the entire mouse olfactory epithelium and single mouse olfactory sensory neurons, Aim 1 will clarify how trigeminal activation by an irritant can modify the olfactory response to an odorant and will analyze how this affects responses of single and populations of OSNs. The trigeminal potency of each odorant will be determined, clarifying whether this characteristic has a significant impact on modulation of the olfactory response and its temporal dynamic. Aim 2 will address ATP signaling in the olfactory epithelium, determining trigeminal ATP kinetics in response to odorants with different trigeminal potencies and the role of ATP in modulating the odorant-evoked action potential firing of single OSNs. ATP will be measured using an ATP biosensor. Aim 2 will also determine the role of purinergic currents in olfactory response reduction by irritants, using single OSN recordings from the intact olfactory epithelium. This project will thus provide a more accurate understanding of the role of the trigeminal system as an integral player, together with the olfactory system, in olfactory perception. It will also fill large gaps in our current understanding of a range of poorly understood mechanisms, including perfumery and food preferences and odor and flavor persistence. And it will contribute to understanding the physiology behind pathological variations of olfactory sensitivity, induced by trigeminal activation due to, for example, smoking, hazardous work enviroment or migraine.

项目摘要 嗅觉和三叉系统通常被认为是独立的，但大多数气味都激活了 三叉神经系统和大多数刺激物激活嗅觉感觉神经元（OSN）。这两个系统共定位 在嗅觉上皮和灯泡以及不同的皮质区域。三叉神经刺激通常会减少 气味强度感知，但尚未确定沿嗅觉途径的抑制 发生或涉及哪些生理机制。嗅觉上皮，嗅觉 响应是首先产生的，是候选这种相互作用的候选基因座。在这里，OSN被密集散布 带有三叉神经肽纤维。这些纤维可以被大多数气味剂激活，它们可以释放 不同的神经肽和ATP。这些物质可以介导炎症反应，但也可以 扮演其他角色。特别是，ATP是一个重要的细胞外信号分子，与 周围和中枢神经系统以及外围味道系统中的神经传递。 ATP敏感受体在OSN和三叉肽纤维上的嗅觉上皮中都发现。 但是，外周三叉富尔科互动和ATP作为介体的潜在作用尚未 被研究。使用来自整个小鼠嗅觉上皮的电生理记录和单个 小鼠嗅觉神经元，AIM 1将阐明刺激物的三叉神经激活如何改变 嗅觉反应对气味剂，并将分析这如何影响OSN的单个和种群的响应。 将确定每种气味的三叉神经效力，阐明此特征是否具有 对嗅觉响应及其时间动态的调节的显着影响。 AIM 2将解决ATP 嗅觉上皮中的信号传导，确定三叉神经动力学，以响应具有的气味剂 不同的三叉神经效应和ATP在调节气味诱发的动作电势触发中的作用 单个OSN。 ATP将使用ATP生物传感器测量。 AIM 2还将决定嘌呤能的作用 使用完整嗅觉的单一OSN记录，刺激性降低嗅觉响应的电流减少了 上皮。因此 嗅觉感知中的整体播放器与嗅觉系统一起。它也会填补我们的大空白 当前对一系列知识较低的机制的理解，包括香水和食物偏好 以及气味和风味持久性。它将有助于理解病理背后的生理 嗅觉敏感性的变化，由于吸烟，危险而引起的三叉神经激活引起 工作环境或偏头痛。