Trigeminal Modulation of Olfactory Responses in the Main Olfactory Epithelium

项目总结 嗅觉和三叉神经系统通常被认为是独立的，但大多数气味会激活 三叉神经系统，大多数刺激物激活嗅觉感觉神经元。这两个系统共同本地化 在嗅觉上皮和嗅球以及不同的皮质区域。三叉神经刺激通常会减少 气味强度知觉，但还没有确定这种抑制沿嗅觉通路的位置 发生或涉及哪些生理机制。嗅觉上皮，嗅觉 反应是最先产生的，是承载这种相互作用的候选基因。在这里，OSN密集分布 三叉神经肽能纤维。这些纤维可以被大多数气味物质激活，它们可以释放 不同的神经肽和三磷酸腺苷。这些物质可以调节炎症反应，但它们也可以 扮演其他角色。特别是，ATP是一种重要的胞外信号分子，它参与了 外周和中枢神经系统以及外周味觉系统的神经传递。 ATP敏感受体存在于嗅觉上皮、嗅核和三叉神经肽能纤维上。 然而，外周三叉神经-嗅觉的相互作用以及三磷酸腺苷作为其介体的潜在作用并没有 已经研究过了。使用整个小鼠嗅觉上皮和单个嗅觉上皮的电生理记录 小鼠嗅觉感觉神经元，Aim 1将阐明刺激物激活三叉神经如何改变 嗅觉对气味的反应，并将分析这如何影响单个和群体的OSN的反应。 每种气味的三叉神经效力将被确定，以澄清这一特征是否具有 对嗅觉反应的调制及其时间动态有显著影响。目标2将解决ATP问题 嗅觉上皮信号，确定三叉神经三叉神经三磷酸腺苷对气味的反应动力学 三叉神经不同电位及三磷酸腺苷对嗅觉诱发动作电位放电的调节作用 单个OSN。将使用三磷酸腺苷生物传感器测量三磷酸腺苷。目标2还将确定嘌呤能 使用来自完整嗅觉的单个OSN记录，刺激物减少嗅觉反应的电流 上皮组织。因此，该项目将更准确地了解三叉神经系统在 与嗅觉系统一起，在嗅觉中发挥着不可或缺的作用。它还将填补我们在 目前对一系列知之甚少的机制的了解，包括香水和食物偏好 以及气味和味道的持久性。这将有助于理解病理性背后的生理学 嗅觉敏感度的变化，由三叉神经激活引起，例如，吸烟，危险 工作环境或偏头痛。

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.