Chronic 40 Hz light flicker mitigates epileptogenesis through a visual pathway associated with the dorsal lateral geniculate nucleus shell

Lei Wang, Wenhao Xu, Kai Wang, Jinwei Yang, Hanli Li, Qi Wang, Zhong Dong, Xiaoyu Zhang, Qian Meng, Fengqing Lu, Jianxiang Lei, Yujing Yang, Kai Wang (), Lijie Feng () and Yu Wang ()
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Lei Wang: the First Affiliated Hospital of Anhui Medical University
Wenhao Xu: the First Affiliated Hospital of Anhui Medical University
Kai Wang: the First Affiliated Hospital of Anhui Medical University
Jinwei Yang: the First Affiliated Hospital of Anhui Medical University
Hanli Li: the First Affiliated Hospital of Anhui Medical University
Qi Wang: the First Affiliated Hospital of Anhui Medical University
Zhong Dong: the First Affiliated Hospital of Anhui Medical University
Xiaoyu Zhang: the First Affiliated Hospital of Anhui Medical University
Qian Meng: the First Affiliated Hospital of Anhui Medical University
Fengqing Lu: the First Affiliated Hospital of Anhui Medical University
Jianxiang Lei: the First Affiliated Hospital of Anhui Medical University
Yujing Yang: the First Affiliated Hospital of Anhui Medical University
Kai Wang: the First Affiliated Hospital of Anhui Medical University
Lijie Feng: Anhui Medical University
Yu Wang: the First Affiliated Hospital of Anhui Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Altered gamma activity is associated with epilepsy. Gamma entrainment using sensory stimuli (GENUS), a non-invasive, exogenous stimulation by rhythmic 40 Hz light flicker, strengthens gamma activity in the primary visual cortex (V1) and suppresses spike generation. Here, we assessed the effect of GENUS on epileptogenesis in male mice with status epilepticus induced by pilocarpine. We found that GENUS immediately increased gamma activity and reduced epileptiform spikes in epileptic mice. After six weeks of GENUS treatment in epileptic mice, significant reductions were observed in neuronal loss and gliosis, brain hyperexcitability was ameliorated, and epilepsy-related behavioral performance was improved. We determined that the increased 40 Hz oscillations and reduced seizure susceptibility induced by GENUS were dependent on the visual circuit associated with ON-OFF direction-selective retinal ganglion cells, glutamatergic neurons in the shell of the dorsal lateral geniculate nucleus, and parvalbumin-expressing fast-spiking interneurons in the superficial 2/3 layer of V1.

Date: 2025
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DOI: 10.1038/s41467-025-64269-2

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