School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia.
Brain Behav. 2023 Aug;13(8):e3064. doi: 10.1002/brb3.3064. Epub 2023 Jul 3.
The efferent vestibular system (EVS) is a feedback circuit thought to modulate vestibular afferent activity by inhibiting type II hair cells and exciting calyx-bearing afferents in the peripheral vestibular organs. In a previous study, we suggested EVS activity may contribute to the effects of motion sickness. To determine an association between motion sickness and EVS activity, we examined the effects of provocative motion (PM) on c-Fos expression in brainstem efferent vestibular nucleus (EVN) neurons that are the source of efferent innervation in the peripheral vestibular organs.
c-Fos is an immediate early gene product expressed in stimulated neurons and is a well-established marker of neuronal activation. To study the effects of PM, young adult C57/BL6 wild-type (WT), aged WT, and young adult transgenic Chat-gCaMP6 mice were exposed to PM, and tail temperature (T ) was monitored using infrared imaging. After PM, we used immunohistochemistry to label EVN neurons to determine any changes in c-Fos expression. All tissue was imaged using laser scanning confocal microscopy.
Infrared recording of T during PM indicated that young adult WT and transgenic mice displayed a typical motion sickness response (tail warming), but not in aged WT mice. Similarly, brainstem EVN neurons showed increased expression of c-Fos protein after PM in young adult WT and transgenic mice but not in aged cohorts.
We present evidence that motion sickness symptoms and increased activation of EVN neurons occur in young adult WT and transgenic mice in response to PM. In contrast, aged WT mice showed no signs of motion sickness and no change in c-Fos expression when exposed to the same provocative stimulus.
传出前庭系统（EVS）是一个反馈回路，被认为通过抑制 II 型毛细胞和兴奋外周前庭器官中的有盖纤维传入神经来调节前庭传入活动。在之前的研究中，我们提出 EVS 活动可能有助于晕动病的发生。为了确定晕动病与 EVS 活动之间的关联，我们研究了刺激性运动（PM）对脑干传出前庭核（EVN）神经元中 c-Fos 表达的影响，这些神经元是外周前庭器官传出神经支配的来源。
c-Fos 是一种在受刺激的神经元中表达的即时早期基因产物，是神经元激活的良好标志物。为了研究 PM 的影响，年轻成年 C57/BL6 野生型（WT）、老年 WT 和年轻成年转基因 Chat-gCaMP6 小鼠接受 PM 刺激，并使用红外成像监测尾巴温度（T）。PM 后，我们使用免疫组织化学标记 EVN 神经元，以确定 c-Fos 表达的任何变化。所有组织均使用激光扫描共聚焦显微镜进行成像。
PM 期间 T 的红外记录表明，年轻成年 WT 和转基因小鼠表现出典型的晕动病反应（尾巴变暖），但老年 WT 小鼠没有。同样，年轻成年 WT 和转基因小鼠的脑干 EVN 神经元在 PM 后显示 c-Fos 蛋白表达增加，但老年组没有。
我们提供的证据表明，年轻成年 WT 和转基因小鼠在 PM 刺激下出现晕动病症状和 EVN 神经元激活增加。相比之下，老年 WT 小鼠在暴露于相同刺激性刺激时没有出现晕动病症状，也没有 c-Fos 表达的变化。
