Neural signature of chronic migraine mice model and related photophobia in the primary visual cortex.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.