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bioRxiv · 10.64898/2026.04.12.717984

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

Xie, Z.·Pan, L.·Hua, Y.·Hou, B.·Xiang, P.·Wu, Y.·Shan, S.·Yan, X.·Chen, Y.·Gao, P.·Du, J.·Liu, J.
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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 980 nm NIR illumination initiates neuronal excitation, which will remain excited without further stimulation but will be rapidly terminated on demand by a subsequent 808 nm illumination. Upon transcranial 980 nm and 808 nm 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.

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Xie, Z., Pan, L., Hua, Y., Hou, B., Xiang, P., Wu, Y., Shan, S., Yan, X., Chen, Y., Gao, P., Du, J., Liu, J.. 2026-04-15. An orthogonal near-infrared optical switch for wireless neuromodulation in freely behaving mice. https://doi.org/10.64898/2026.04.12.717984

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