PBS R1 and R2 LFP recordings.

The olfactory system is exposed to external and internal harmful agents that may impair the communication between the olfactory sensory neurons and olfactory brain areas. Inflammatory molecules increase in the olfactory system in response to infections and chronic systemic diseases. Interleukin-1β (IL-1β) is a cytokine produced in many inflammatory processes. In previous studies, we observed that IL-1β increased in the olfactory bulb (OB) of diabetic rats, which also presented olfactory dysfunction. This study aimed to determine whether IL-1β could be responsible for the olfactory impairment. To address this question, IL-1β and its antagonist IL-1Ra were microinjected in the OB of rats to evaluate the electrophysiological activity in the OB and entorhinal cortex (EC) by recording the local field potentials (LFPs) in resting conditions and during olfactory stimulation. RNA-seq analysis from NCBI databases demonstrated the expression of IL-1β receptor 1 (IL1-R1) in the OB from rats and mice. Interestingly, IL-1β reduced total spectral power in the OB and increased total signal frequency and gamma power in both OB and EC. Moreover, IL-1β reduced the amplitude and increased the latency of the olfactory evoked potentials (OEPs) after OB stimulation with amyl acetate. IL-1Ra microinjection before IL-1β rescued amplitude and latency of OEPs, but only partially reverted the effects of IL-1β in total spectral power and relative gamma power. In addition, IL-1Ra changed the electrophysiological activity of OB and EC; however, its effect was lower than that of IL-1β. These results suggest that IL-1β may induce olfactory dysfunction by suppressing neuronal activity in the OB and EC. Furthermore, IL-1β may also have a physiological role in the olfactory system since IL-1Ra can modify the electrical activity in these brain areas.嗅觉系统会暴露于外源性与内源性有害因子，此类因子可能损害嗅觉感觉神经元与嗅觉脑区之间的信号传递。机体针对感染及慢性全身性疾病产生应答时，嗅觉系统内的炎症分子水平会升高。白细胞介素-1β（Interleukin-1β, IL-1β）是多种炎症过程中产生的细胞因子。在既往研究中，我们观察到糖尿病大鼠的嗅球（Olfactory Bulb, OB）中IL-1β水平升高，且此类大鼠同时表现出嗅觉功能障碍。本研究旨在明确IL-1β是否为嗅觉功能受损的诱因。为解答该问题，我们向大鼠嗅球显微注射IL-1β及其拮抗剂IL-1Ra，通过记录静息状态与嗅觉刺激过程中的局部场电位（Local Field Potentials, LFPs），评估嗅球与内嗅皮层（Entorhinal Cortex, EC）的电生理活动。NCBI数据库的RNA-seq分析显示，大鼠与小鼠的嗅球中均表达白细胞介素-1β受体1（Interleukin-1β Receptor 1, IL1-R1）。值得注意的是，IL-1β会降低嗅球的总频谱功率，同时升高嗅球与内嗅皮层的总信号频率与伽马功率。此外，经乙酸戊酯刺激嗅球后，IL-1β会降低嗅觉诱发电位（Olfactory Evoked Potentials, OEPs）的振幅，并延长其潜伏期。在给予IL-1β前通过显微注射IL-1Ra预处理的大鼠，可恢复嗅觉诱发电位的振幅与潜伏期，但仅能部分逆转IL-1β对总频谱功率与相对伽马功率的影响。此外，IL-1Ra可改变嗅球与内嗅皮层的电生理活动，但其作用强度弱于IL-1β。上述结果表明，IL-1β可能通过抑制嗅球与内嗅皮层的神经元活性，诱导嗅觉功能障碍。此外，鉴于IL-1Ra可调控上述脑区的电生理活动，IL-1β在嗅觉系统中或也具有生理调控作用。