Zhang Kai-Bo, Peng Cheng, Liu Zhen, Zhao Sheng-Lin, Zhu Chen-Lu, Wu Shou-Yi, Wang Tian-Xiao, Li Zhi-Lei, Gao Jing-Gui, Xu Yun-Hao, Fan Tian-Hua, Xie Hong, Guan Ji-Song, Wang Yong-Gang
Department of Neurology, Lanzhou University Second Hospital, Cuiying Gate, No. 82 Linxia Road, Chengguan District, Lanzhou, 730000, China.
School of Life Science and Technology & State Key Laboratory of Advanced Medical Materials and Device, ShanghaiTech University, No.393 Middle Huaxia Road, Pudong District, Shanghai, 201210, China.
J Headache Pain. 2025 Aug 12;26(1):182. doi: 10.1186/s10194-025-02123-y.
Migraine episodes are known to induce heightened photosensitivity. Neuroimaging investigations have revealed that the primary visual cortex exhibits abnormal activation patterns both during and between migraine attacks. Growing evidence suggests that altered cortical activity patterns may underlie the pathophysiology of neurological disorders. This study explored whether and how chronic migraine affects cortical activity patterns at single-cell resolution in the primary visual cortex during its progression.
Longitudinal in vivo two-photon calcium imaging was performed in the primary visual cortex of a chronic migraine mouse model across multiple time points. Cortical circuit activity patterns and behavioral correlates were assessed through combined chemogenetic manipulation and pharmacological interventions, with a particular focus on primary visual cortex functional modulation.
Following chronic migraine induction, spontaneous hyperactivation emerged in cortical activity patterns within the primary visual cortex. Layer II/III neurons appeared as major contributors to this neural dysregulation, with layer V neurons showing less pronounced involvement. Prophylactic topiramate treatment attenuated allodynia and light aversion behaviors while reducing pathological cortical hyperactivity. Chemogenetic inhibition of primary visual cortex layer II/III neurons ameliorated light aversion without attenuating pain sensitization, while modulating aberrant spontaneous cortical activity patterns.
These findings provide preliminary evidence for dynamic alterations in spontaneous cortical neural signatures within the primary visual cortex throughout chronic migraine progression. Modulation of these neural adaptations appears to show the potential to alleviate associated light sensitivity, providing insight into potential pathophysiological mechanisms underlying light sensitivity in chronic migraine.
已知偏头痛发作会导致光敏感性增强。神经影像学研究表明,在偏头痛发作期间及发作间期,初级视觉皮层均表现出异常的激活模式。越来越多的证据表明,皮层活动模式的改变可能是神经系统疾病病理生理学的基础。本研究探讨了慢性偏头痛在进展过程中是否以及如何以单细胞分辨率影响初级视觉皮层的皮层活动模式。
在慢性偏头痛小鼠模型的初级视觉皮层中,于多个时间点进行纵向体内双光子钙成像。通过化学遗传操作和药物干预相结合来评估皮层回路活动模式及行为相关性,特别关注初级视觉皮层的功能调制。
在诱导慢性偏头痛后,初级视觉皮层内的皮层活动模式出现自发的过度激活。II/III层神经元似乎是这种神经调节异常的主要促成因素,V层神经元的参与程度则不太明显。预防性托吡酯治疗减轻了异常性疼痛和畏光行为,同时减少了病理性皮层过度活动。对初级视觉皮层II/III层神经元进行化学遗传抑制可改善畏光现象,而不会减轻疼痛敏化,同时调节异常的自发皮层活动模式。
这些发现为慢性偏头痛进展过程中初级视觉皮层内自发皮层神经特征的动态变化提供了初步证据。对这些神经适应性的调节似乎显示出减轻相关光敏感性的潜力,为慢性偏头痛光敏感性潜在的病理生理机制提供了见解。