Neural mechanisms of the V2M-PrL pathway mediate blue light-induced spatial memory impairment.

Blue light has been shown to impair spatial memory in mice. However, the underlying neural circuit mechanisms of this impairment remain elusive. Our study revealed that 600-lux blue light disrupted spatial memory retrieval in male mice through the secondary visual cortex (V2M) → the prelimbic cortex (PrL) neural pathway. Specifically, viral tracing and multichannel fiber optic recordings demonstrated that glutamatergic V2M neurons (V2M(Glu)) projected to GABAergic neurons in the PrL (PrL(GABA)), thereby inhibiting the excitability of glutamatergic PrL neurons (V2M(Glu)→PrL(GABA→Glu)). The selective ablation of V2M(Glu) neurons projecting to the PrL eliminated the detrimental effects of blue light on spatial memory retrieval. Furthermore, optogenetic or chemogenetic activation of the V2M(Glu) → PrL(GABA→Glu) neural circuitry replicated the impairing effects of blue light on spatial memory in mice. Conversely, inhibition of the V2M(Glu) → PrL(GABA→Glu) neural circuitry reversed the spatial memory damage induced by blue light. Collectively, our findings elucidate the V2M(Glu) → PrL(GABA→Glu) neural circuitry as a potential mediator of blue-light-induced spatial memory impairment in male mice.