Non-invasive, opsin-free mid-infrared modulation activates cortical neurons and accelerates associative learning

Abstract Neurostimulant drugs or magnetic/electrical stimulation techniques can overcome attention deficits, but these are weakly beneficial in boosting the learning capabilities of healthy subjects. Here, we report a technique, mid-infrared modulation (MIM), that delivers light energy through opened skull even non-invasively thinned intact and activate brain neurons vivo without introducing any exogeneous gene. Using c-Fos immunohistochemistry, single-cell electrophysiology two-photon Ca 2+ imaging mice, demonstrate MIM significantly induces firing activities targeted cortical area. Moreover, mice receive targeting to auditory cortex during an associative task exhibit faster speed (~50% faster) than control mice. Together, this non-invasive, opsin-free technique is demonstrated with potential for modulating neuronal activity.