前扣带皮层谷氨酸能投射神经元通过皮层-前庭环路调节运动病易感性

文献信息

中文摘要

背景： 运动病（MS）是一种常见且使人衰弱的前庭疾病，治疗选择有限，但控制个体易感性的皮层机制仍不清楚。方法：使用双轴旋转小鼠模型，我们通过整合形态学、钙成像、电生理学、细胞消融、化学遗传学和光遗传学，研究了前扣带皮层（ACC）在MS中的作用。结果：双轴旋转诱导了低体温、厌食、味觉回避、运动活动减少和步态不协调。前庭刺激后，ACC锥体神经元表现出增强的激活和增加的内在兴奋性。消融ACC CaMKII+神经元减轻了MS症状，双向化学遗传学操作表明ACC谷氨酸能投射神经元对MS行为既是必要的也是充分的。此外，ACC到内侧前庭核小细胞部（MVePC）的投射被确定为一个先前未表征的皮层-前庭环路，双向介导MS易感性。全脑投射组分析进一步揭示了ACC-内侧前庭神经元的解剖异质性投射亚型。结论：这些发现推进了我们对MS皮层机制的理解，并将ACC-MVePC通路确立为未来神经调控策略的机制切入点。

英文摘要

Motion sickness (MS) is a prevalent and debilitating vestibular disorder with limited therapeutic options, yet the cortical mechanisms governing individual susceptibility remain elusive. Using a biaxial rotation mouse model, we investigated the role of the anterior cingulate cortex (ACC) in MS by integrating morphology, calcium imaging, electrophysiology, cell ablation, chemogenetics, and optogenetics. Biaxial rotation induced hypothermia, anorexia, taste avoidance, locomotor hypoactivity, and gait incoordination. ACC pyramidal neurons exhibited enhanced activation and increased intrinsic excitability following vestibular stimulation. Ablation of ACC CaMKII+ neurons alleviated MS symptoms, and bidirectional chemogenetic manipulation demonstrated that ACC glutamatergic projection neurons are both necessary and sufficient for MS behaviors. Furthermore, the ACC to medial vestibular nuclei parvicellular part (MVePC) projection was identified as a previously uncharacterized cortico-vestibular circuit that bidirectionally mediates MS susceptibility. Whole-brain projectome analysis further revealed anatomically heterogeneous projection subtypes of ACC-medial vestibular neurons. These findings advance our understanding of the cortical mechanisms underlying MS and establish the ACC-MVePC pathway as a mechanistic entry point for future neuromodulatory strategies.