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: 10318988
• 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 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10318988
• 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; antagonist; 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 嗅觉系统和三叉神经系统通常被认为是独立的，但大多数气味剂激活 大多数刺激物激活嗅觉感觉神经元（OSN）。这两个系统共同定位 在嗅上皮和嗅球以及不同的皮层区域。三叉神经刺激通常会减少 气味强度感知，但它尚未建立在沿着嗅觉通路这种抑制 发生或涉及哪些生理机制。嗅觉上皮， 响应首先被生成，是一个候选基因座，以窝藏这种相互作用。在这里，OSN密集地散布 三叉神经肽能纤维这些纤维可以被大多数气味激活，它们可以释放出 不同的神经肽和ATP。这些物质可以介导炎症反应，但它们也可以 扮演其他角色。特别地，ATP是一种重要的细胞外信号分子，其参与 在外周和中枢神经系统以及外周味觉系统中的神经传递。 在嗅上皮中，在OSN和三叉神经肽能纤维上发现ATP敏感受体。 然而，外周三叉神经-嗅觉相互作用和ATP作为其介质的潜在作用还没有 本文研究了使用整个小鼠嗅上皮和单个 小鼠嗅觉感觉神经元，目标1将阐明刺激物如何激活三叉神经可以修改 嗅觉反应的气味，并将分析如何影响反应的单一和人口的OSN。 将确定每种气味剂的三叉神经效力，澄清这种特性是否具有 显著影响嗅觉反应的调制及其时间动态。目标2将解决ATP 嗅觉上皮中的信号传导，确定三叉神经ATP动力学对气味剂的反应， 不同的三叉神经电位和ATP在调节气味诱发的动作电位放电中的作用 单个OSN。将使用ATP生物传感器测量ATP。目的2也将确定嘌呤能的作用 刺激物引起的嗅觉反应降低的电流，使用来自完整嗅觉的单OSN记录 上皮因此，该项目将提供对三叉神经系统的作用的更准确的理解， 一个完整的球员，连同嗅觉系统，在嗅觉感知。它也将填补我们在这方面的巨大空白。 目前对一系列知之甚少的机制的理解，包括香水和食物偏好 以及气味和风味的持久性。这将有助于理解病理性疾病背后的生理学 嗅觉灵敏度的变化，由三叉神经激活引起，例如，吸烟，危险 工作环境或偏头痛。

项目成果

Sensory Transduction in Photoreceptors and Olfactory Sensory Neurons: Common Features and Distinct Characteristics.

• DOI: 10.3389/fncel.2021.761416
• 发表时间: 2021
• 期刊: Frontiers in cellular neuroscience
• 影响因子: 5.3
• 作者: Genovese F;Reisert J;Kefalov VJ
• 通讯作者: Kefalov VJ

The functional relevance of olfactory marker protein in the vertebrate olfactory system: a never-ending story.

• DOI: 10.1007/s00441-020-03349-9
• 发表时间: 2021-01
• 期刊: Cell and tissue research
• 影响因子: 3.6
• 作者: Dibattista M;Al Koborssy D;Genovese F;Reisert J
• 通讯作者: Reisert J

Assessing the extent and timing of chemosensory impairments during COVID-19 pandemic.

• DOI: 10.1038/s41598-021-96987-0
• 发表时间: 2021-09-01
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Cecchetto C;Di Pizio A;Genovese F;Calcinoni O;Macchi A;Dunkel A;Ohla K;Spinelli S;Farruggia MC;Joseph PV;Menini A;Cantone E;Dinnella C;Cecchini MP;D'Errico A;Mucignat-Caretta C;Parma V;Dibattista M
• 通讯作者: Dibattista M