Near-Infrared-II Chemo-Optogenetics for Deep-Brain Stimulation

We introduced a near-infrared II (NIR-II)-mediated optogenetic neuromodulation inspired by HaloTag self-labelling system (HaloNeu). An engineered temperature-sensitive ion channel HaloTag-TRPV1 was developed and stably targeted activation through NIR-II photothermal conversion nanoparticles functionalized with HaloTag chloroalkane ligands in vivo by irreversible covalent bond formation. This allowed non-invasive, long-term stable and cell-type specific neuromodulation and behavioral manipulation by low and safe power of NIR-II illumination. Moreover, the HaloNeu approach enables precise activation of VTA-triggered neural circuits, offering effective and stable intervention on symptoms of Parkinson’s disease (PD).