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An orthogonal near-infrared optical switch for wireless neuromodulation in freely behaving mice

Created on 16 Apr 2026

Authors

Xie, Z., Pan, L., Hua, Y., Hou, B., Xiang, P., Wu, Y., Shan, S., Yan, X., Chen, Y., Gao, P., Du, J., Liu, J.

Abstract

Modulating neuronal activity with light is a powerful tool for neuroscience research. However, currently available technologies often require invasive fibers for delivery of visible light, causing tissue damage and limiting behavioral studies. Although near-infrared (NIR) neuronal modulation improves tissue penetration depth, sustained NIR illumination during neuromodulation raises significant concerns about photothermal effects. Here, we introduce a dual-wavelength near-infrared switch (Dual-NIR Switch) that uses two transcranial NIR inputs to initiate and terminate neuronal activation, enabling tether-free neuromodulation in freely moving mice. Dual-NIR Switch employs orthogonal dichromatic upconversion nanoparticles that emit blue and green light under 980 nm and 808 nm excitation, respectively, to activate and inactivate the step-function opsin SOUL. Therefore, transient 980nm NIR illumination initiates neuronal excitation, which will remain excited without further stimulation but will be rapidly terminated on demand by a subsequent 808nm illumination. Upon transcranial 980nm and 808nm NIR illuminations in freely moving mice, we achieve on-demand control of behavioral paradigms across tunable timescales, ranging from seconds to minutes and even extending to sub-hour durations. By eliminating the need for sustained NIR irradiation, Dual-NIR Switch offers an on-demand, duration-tunable neuromodulation tool for both basic neuroscience and potential therapeutic applications in treating brain diseases.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 16 Apr 2026.

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