Green light relieves stress-induced anxiety-like behaviors via visual-to-prefrontal projections in mice

Green environments have long been recognized to produce calming, anxiolytic effects, although the underlying neural mechanisms remain poorly understood. Here, we find that green light treatment can relieve anxiety-like behaviors by activating a neural pathway from the medial part of the secondary visual cortex (V2M) to the prelimbic cortex (PrL) in mice subjected to acute stress. Viral tracing, fiber photometry, and microendoscopic calcium imaging together show that green light activates glutamatergic inputs from V2M (V2M^Glu) to inhibitory neurons expressing corticotropin-releasing factor in the PrL (PrL^CRF), which in turn suppress local glutamatergic neurons (V2M^Glu→PrL^CRF→Glu). Chemogenetic activation of this pathway mimics the anxiolytic effects of green light, whereas artificial inhibition of this pathway or pharmacological blockade of CRF receptor 1 (CRFR1) in the PrL abolishes green-light-induced anxiolysis in acute stress model mice. This study thus indicates a CRF-dependent neural mechanism underlying the anxiolytic effects of green light under stress conditions.