Instant noninvasive near-infrared deep brain stimulation using optoelectronic nanoparticles without genetic modification

Noninvasive transcranial neuromodulation of deep brain regions is a longstanding goal in neuroscience. While optogenetics enables remote neural control, it is constrained by shallow tissue penetration of visible light and delayed onset due to required opsin expression. Here, we introduce a neuromodulation technique using hybrid upconversion and photovoltaic (HUP) nanoparticles, which eliminates the need for genetic modification and affords near-infrared (NIR) activation of neurons in wild-type mice. This method converts deeply penetrating NIR light into localized electrical stimuli, enabling immediate and precise modulation in deep brain. In vitro patch-clamp experiments confirm neuronal activation upon HUP application. In vivo, we achieve remote NIR neuromodulation in the medial septum and ventral tegmental area 7 days postinjection, effectively modulating neuronal activity, suppressing seizures, and triggering dopamine release. This minimally invasive approach offers a versatile tool kit for investigating neural processes in mammals, with potential applications across diverse brain regions through customizable nanoparticle engineering.