Parvalbumin Interneuron‐Dependent Hippocampal Neurogenesis Evoked by Prolonged Rhythmic Light Flicker

Abstract Rhythmic light flicker alleviates cognitive impairments in various animal models of neurological diseases. However, its long‐term effects and underlying mechanisms remain unclear. Here, a cohort of adult mice is subjected to long‐term exposure to 40 Hz light flicker (1 hour daily for 30 days) and observed significant enhancements in hippocampal neurogenesis and spatial learning without any adverse behavioral effects. Specific ablation of hippocampal newborn neurons using DCX DTR mice abolished these effects. Furthermore, the inactivation or elimination of GABAergic parvalbumin (PV) interneurons not only impaired 40 Hz light flicker entrainment but also reduce neurogenesis in the dentate gyrus (DG). Long‐term flicker exposure increases excitatory input to DG PV interneurons, which enhances PV interneuron excitability, elevated GABA levels, and strengthened inhibitory transmission to newborn neurons, thereby promoting better integration of new neurons into the DG. Blocking GABA A receptors reverse the light flicker‐induced increase in neurogenesis and spatial learning. Prolonged flicker exposure do not affect DG regional cerebral blood flow or the activity of excitatory cholinergic, vasoactive intestinal peptide (VIP), or cholecystokinin (CCK) interneurons. These findings suggest that long‐term light flicker enhances spatial learning through PV‐dependent neurogenesis, with elevated GABAergic activity supporting the development and integration of immature neurons in the adult DG.