Non-invasive light flickering reinstates visual plasticity in adult mice via lipocalin 2.

BACKGROUND: Light flickering, a non-invasive stimulation technique over recent years, has shown a promising therapeutic potential for brain dysfunctions. However, the mechanisms by which this visual stimulus exerts its beneficial effects are largely unknown. RESULTS: Here, we found that 7 days of 1 h 20 and 40 Hz light flickering promoted visual plasticity in primary visual cortex of adult mice. RNA sequencing results showed an increase in lipocalin 2 (LCN2) expression in the visual cortex following 20 or 40 Hz light flickering. By contrast, 80 Hz light flickering or constant light had no significant effect on either plasticity or LCN2 expression. LCN2 knock-down blocked light flickering-induced plasticity, while its overexpression mimicked the effects of light flickering. Moreover, the administration of minocycline blocked the plasticity induced by either light flickering or LCN2 overexpressing. Lastly, 40 Hz light flickering combined with reverse suture facilitated the recovery of the abnormal ocular dominance distribution in adult amblyopic mice. CONCLUSIONS: Our data indicate that non-invasive light flickering restores visual plasticity, mediated by LCN2 and microglia, providing new insights into the mechanism of light flickering.