Photo‐Biomodulation of the Hippocampus Using Near‐Infrared Laser to Enhance Cognitive Function in Mice

Abstract Photo‐biomodulation (PBM) with near‐infrared (NIR) laser emerges as a promising noninvasive therapy for enhancing cognitive function. Here the effects of PBM, equipped with an 808 nm NIR laser, on cognitive function are investigated when used to irradiate hippocampi of mice. NIR irradiation once a day for 5 min per day for 5 consecutive days significantly improves the learning and memory performance of naïve mice assessed with the Barnes and Y maze tests. PBM also significantly attenuates cognitive dysfunction following anesthesia and surgery, and lipopolysaccharide challenge, respectively. Cognitive enhancements are associated with increased neuronal oscillations and enhanced theta–gamma coupling in the hippocampal dentate gyrus (DG) during cognitive processing. High neuronal activation in the DG is evidenced by increased c‐Fos expression and calcium signal intensity. The improvements are also associated with high‐density cells in the DG together with facilitating local energy deposition and neuronal activation. NIR‐laser‐activated axonogenesis and oxidative phosphorylation‐related genes assessed with single‐cell RNA sequencing were seen in the DG. These findings suggest that PBM very likely holds great potential as a noninvasive therapy for cognitive dysfunction.