Transcranial and precise optical neuromodulation mediated by NIR photoactive nanosheets

Remote modulation of specific neurons is critical for neural circuit dissection and neurological disease therapy. Traditional neuromodulation strategies applying electrodes and external stimuli may suffer from invasive injuries and insufficient spatiotemporal resolution, respectively. Herein, transcranial optical neuromodulation with precise spatiotemporal control was realized by establishing a nanophotonic neural interface, where the polyethylene glycol-modified two-dimensional Ti₃C₂T_x (MXene) served as near-infrared (NIR) photoactive nanosheets (PANS). Polymer modification of the nanosheets contributed to a robust PANS-neuron interface, which allowed efficient modulation of non-transgenic neurons with subcellular resolution and millisecond precision. The PANS-enabled transcranial optical neuromodulation not only evoked neuronal action potentials in brain slices with a high synchronization rate of 98.33%, but also facilitated neuronal firing in vivo. With PANS as stimulus targets, the transcranial NIR light can excite neurons in desired brain regions and activate defined neural circuits, thus regulating mouse behaviors with minimal invasiveness. Such nanosheet-enabled transcranial and precise optical neuromodulation, eliminating invasive implants and genetic manipulation, may open opportunities for neurophotonics and neuroscience research. Transcranial optical neuromodulation with precise spatiotemporal control was realized via a nano-enabled optical neural interface, where the polyethylene glycol-modified two-dimensional Ti₃C₂T_x serves as near-infrared photoactive nanosheets. Such efficient neuromodulation of non-transgenic animals with subcellular resolution and millisecond precision, eliminating invasive implants and genetic manipulation, holds potential for neuroscience research.