{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:14:26Z","timestamp":1786547666040,"version":"build-2736575974"},"reference-count":55,"publisher":"American Chemical Society (ACS)","issue":"31","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32271144"],"award-info":[{"award-number":["32271144"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chinese Academy of Sciences Project for Young Scientists in Basic Research","award":["YSBR-139"],"award-info":[{"award-number":["YSBR-139"]}]},{"name":"STI2030-Major Projects","award":["2021ZD0202200"],"award-info":[{"award-number":["2021ZD0202200"]}]},{"name":"STI2030-Major Projects","award":["2021ZD0202203"],"award-info":[{"award-number":["2021ZD0202203"]}]},{"name":"Lingang Laboratory Grant","award":["LG-QS-202202-03"],"award-info":[{"award-number":["LG-QS-202202-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Modulating neuronal activity with light is a powerful tool for neuroscience research. However, currently available technologies often require invasive fibers for the 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. The Dual-NIR Switch employs orthogonal dichromatic upconversion nanoparticles that emit blue and green light under 980 and 808 nm NIR excitation, respectively, to activate and inactivate the step-function opsin SOUL. Therefore, transient 980 nm NIR illumination initiates neuronal excitation that persists without further stimulation and can be rapidly terminated on demand by subsequent 808 nm NIR illumination. Upon sequential transcranial 980 and 808 nm NIR illumination in freely moving mice, we achieve on-demand control of behavioral paradigms across tunable time scales, ranging from seconds to minutes and even extending to subhour durations. By eliminating the need for sustained NIR irradiation, the Dual-NIR Switch offers an on-demand, duration-tunable neuromodulation tool for both basic neuroscience and potential therapeutic applications in treating brain diseases.<\/jats:p>","DOI":"10.1021\/jacs.6c07856","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:04:31Z","timestamp":1785852271000},"page":"33352-33363","source":"Crossref","is-referenced-by-count":0,"title":["An Orthogonal Near-Infrared\nOptical Switch for Wireless\nNeuromodulation in Freely Behaving Mice"],"prefix":"10.1021","volume":"148","author":[{"given":"Zheyu","family":"Xie","sequence":"first","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9176-6647","authenticated-orcid":true,"given":"Limin","family":"Pan","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yipeng","family":"Hua","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]},{"name":"ShanghaiTech University , , ,","place":["Shanghai, China, 201210"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojun","family":"Hou","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peishan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifang","family":"Shan","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximei","family":"Yan","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fajuan","family":"Tian","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Chen","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]},{"name":"ShanghaiTech University , , ,","place":["Shanghai, China, 201210"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peizhe","family":"Gao","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Hua","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiulin","family":"Du","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, China, 100049"]},{"name":"ShanghaiTech University , , ,","place":["Shanghai, China, 201210"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2953-4562","authenticated-orcid":true,"given":"Jianan","family":"Liu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Shanghai, China, 200031"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"2026081210082667600_cit1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1146\/annurev-neuro-061010-113817","article-title":"The Development\nand Application of\nOptogenetics","volume":"34","author":"Fenno","year":"2011","journal-title":"Annu. Rev. Neurosci."},{"issue":"7987","key":"2026081210082667600_cit2","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/s41586-023-06715-z","article-title":"Neural Landscape Diffusion Resolves\nConflicts between Needs across\nTime","volume":"623","author":"Richman","year":"2023","journal-title":"Nature"},{"issue":"4","key":"2026081210082667600_cit3","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/nrn.2017.15","article-title":"Integration\nof Optogenetics with\nComplementary Methodologies in Systems Neuroscience","volume":"18","author":"Kim","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"issue":"11","key":"2026081210082667600_cit4","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1038\/s41551-017-0154-1","article-title":"Glial Responses\nto Implanted Electrodes in the Brain","volume":"1","author":"Salatino","year":"2017","journal-title":"Nat. Biomed.\nEng."},{"issue":"10","key":"2026081210082667600_cit5","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1038\/nmeth.3536","article-title":"Wirelessly powered,\nFully Internal\nOptogenetics for Brain, Spinal and Peripheral Circuits in Mice","volume":"12","author":"Montgomery","year":"2015","journal-title":"Nat. Methods"},{"issue":"3","key":"2026081210082667600_cit6","doi-asserted-by":"publisher","first-page":"2209324","DOI":"10.1002\/adma.202209324","article-title":"Engineering Electrodes\nwith Robust Conducting Hydrogel Coating for\nNeural Recording and Modulation","volume":"35","author":"Zhang","year":"2023","journal-title":"Adv. Mater."},{"issue":"37","key":"2026081210082667600_cit7","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202504372","article-title":"Biomaterial-Based\nFibrous\nImplantable Probes for Tissue-Electronics Interface","volume":"37","author":"Xu","year":"2025","journal-title":"Adv. Mater."},{"issue":"1","key":"2026081210082667600_cit8","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/s41593-025-02127-6","article-title":"Patterned Wireless Transcranial Optogenetics Generates\nArtificial Perception","volume":"29","author":"Wu","year":"2026","journal-title":"Nat. Neurosci."},{"issue":"42","key":"2026081210082667600_cit9","doi-asserted-by":"publisher","first-page":"2303267","DOI":"10.1002\/adma.202303267","article-title":"Illuminating the Brain:\nAdvances and Perspectives in Optoelectronics for Neural Activity Monitoring\nand Modulation","volume":"35","author":"Xu","year":"2023","journal-title":"Adv. Mater."},{"issue":"3","key":"2026081210082667600_cit10","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/nmeth.2836","article-title":"Independent\nOptical Excitation of Distinct Neural Populations","volume":"11","author":"Klapoetke","year":"2014","journal-title":"Nat. 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Commun."},{"issue":"4","key":"2026081210082667600_cit19","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1039\/C6CS00415F","article-title":"Anti-Stokes Shift Luminescent\nMaterials\nfor Bio-Applications","volume":"46","author":"Zhu","year":"2017","journal-title":"Chem. Soc. Rev."},{"issue":"11","key":"2026081210082667600_cit20","doi-asserted-by":"publisher","first-page":"2692","DOI":"10.1021\/acs.accounts.0c00513","article-title":"Lanthanide-Activated\nNanoparticles: A Toolbox for Bioimaging, Therapeutics, and Neuromodulation","volume":"53","author":"Yi","year":"2020","journal-title":"Acc. Chem. Res."},{"issue":"29","key":"2026081210082667600_cit21","doi-asserted-by":"publisher","first-page":"9049","DOI":"10.1021\/jacs.6b05192","article-title":"Semiconducting Polymer\nNanobioconjugates for Targeted Photothermal Activation of Neurons","volume":"138","author":"Lyu","year":"2016","journal-title":"J. Am. Chem. Soc."},{"issue":"6","key":"2026081210082667600_cit22","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1038\/s41551-022-00862-w","article-title":"Tether-Free Photothermal\nDeep-Brain Stimulation in Freely Behaving Mice via Wide-Field Illumination\nin the Near-Infrared-II Window","volume":"6","author":"Wu","year":"2022","journal-title":"Nat. Biomed.\nEng."},{"issue":"7","key":"2026081210082667600_cit23","doi-asserted-by":"publisher","first-page":"2464","DOI":"10.1002\/anie.201510609","article-title":"Filtration Shell Mediated Power Density\nIndependent Orthogonal Excitations\u2013Emissions\nUpconversion Luminescence","volume":"55","author":"Li","year":"2016","journal-title":"Angew. Chem., Int.\nEd."},{"issue":"52","key":"2026081210082667600_cit24","doi-asserted-by":"publisher","first-page":"14419","DOI":"10.1002\/anie.201408219","article-title":"An Upconversion\nNanoparticle with Orthogonal Emissions Using Dual NIR Excitations\nfor Controlled Two-Way Photoswitching","volume":"53","author":"Lai","year":"2014","journal-title":"Angew.\nChem., Int. Ed."},{"issue":"1","key":"2026081210082667600_cit25","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.neuron.2020.03.032","article-title":"An Ultra-Sensitive\nStep-Function Opsin for Minimally Invasive Optogenetic\nStimulation in Mice and Macaques","volume":"107","author":"Gong","year":"2020","journal-title":"Neuron"},{"issue":"27","key":"2026081210082667600_cit26","doi-asserted-by":"publisher","first-page":"11068","DOI":"10.1021\/ja302717u","article-title":"Self-Focusing\nby Ostwald Ripening: A Strategy for Layer-by-Layer Epitaxial Growth\non Upconverting Nanocrystals","volume":"134","author":"Johnson","year":"2012","journal-title":"J. Am. Chem. Soc."},{"issue":"3","key":"2026081210082667600_cit27","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1021\/acs.accounts.5c00555","article-title":"Interface Energy Tuning\nin Lanthanide Upconversion Nanoparticles through a Multilayer Growth\nStrategy","volume":"59","author":"Ming","year":"2026","journal-title":"Acc. Chem. Res."},{"issue":"1","key":"2026081210082667600_cit28","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1021\/acs.chemrev.2c00419","article-title":"The Coming\nof Age of Neodymium: Redefining Its Role in Rare Earth Doped Nanoparticles","volume":"123","author":"Matulionyte","year":"2023","journal-title":"Chem. Rev."},{"issue":"10","key":"2026081210082667600_cit29","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1038\/s41566-022-01042-7","article-title":"Incoherent\nBroadband Mid-Infrared Detection with Lanthanide Nanotransducers","volume":"16","author":"Liang","year":"2022","journal-title":"Nat. Photonics"},{"issue":"2","key":"2026081210082667600_cit30","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1021\/acs.accounts.9b00453","article-title":"Combating Concentration\nQuenching in Upconversion Nanoparticles","volume":"53","author":"Chen","year":"2020","journal-title":"Acc.\nChem. Res."},{"issue":"7363","key":"2026081210082667600_cit31","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/nature10360","article-title":"Neocortical\nExcitation\/Inhibition Balance in Information Processing and Social\nDysfunction","volume":"477","author":"Yizhar","year":"2011","journal-title":"Nature"},{"issue":"17","key":"2026081210082667600_cit32","doi-asserted-by":"publisher","first-page":"7858","DOI":"10.1021\/jacs.0c01025","article-title":"Near-Infrared\nVoltage Nanosensors Enable Real-Time Imaging of Neuronal\nActivities in Mice and Zebrafish","volume":"142","author":"Liu","year":"2020","journal-title":"J. Am. Chem.\nSoc."},{"issue":"43","key":"2026081210082667600_cit33","doi-asserted-by":"publisher","first-page":"2210059","DOI":"10.1002\/adma.202210059","article-title":"Materials for Cell Surface Engineering","volume":"36","author":"Adebowale","year":"2024","journal-title":"Adv. Mater."},{"issue":"3","key":"2026081210082667600_cit34","doi-asserted-by":"publisher","first-page":"2208601","DOI":"10.1002\/adma.202208601","article-title":"Transcranial\nNongenetic\nNeuromodulation via Bioinspired Vesicle-Enabled Precise NIR-II Optical\nStimulation","volume":"35","author":"Zhang","year":"2023","journal-title":"Adv. Mater."},{"issue":"7","key":"2026081210082667600_cit35","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/s41551-018-0230-1","article-title":"Rational Design of\nSilicon Structures for Optically Controlled Multiscale Biointerfaces","volume":"2","author":"Jiang","year":"2018","journal-title":"Nat. Biomed. Eng."},{"issue":"52","key":"2026081210082667600_cit36","doi-asserted-by":"publisher","first-page":"14231","DOI":"10.1523\/JNEUROSCI.3578-07.2007","article-title":"Targeting and Readout Strategies\nfor Fast Optical Neural Control In Vitro and In Vivo","volume":"27","author":"Gradinaru","year":"2007","journal-title":"J. Neurosci."},{"issue":"7","key":"2026081210082667600_cit37","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1038\/s41563-020-00896-y","article-title":"Non-Contact\nLong-Range Magnetic Stimulation\nof Mechanosensitive Ion Channels in Freely Moving Animals","volume":"20","author":"Lee","year":"2021","journal-title":"Nat. Mater."},{"key":"2026081210082667600_cit38","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.27069","article-title":"Magnetothermal Genetic\nDeep Brain Stimulation of Motor\nBehaviors in Awake, Freely Moving Mice","volume":"6","author":"Munshi","year":"2017","journal-title":"Elife"},{"issue":"6669","key":"2026081210082667600_cit39","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1126\/science.adh8287","article-title":"Neurocircuits\nfor Motivation","volume":"382","author":"Stuber","year":"2023","journal-title":"Science"},{"issue":"2","key":"2026081210082667600_cit40","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/nn.4220","article-title":"Lateral Hypothalamic\nCircuits for Feeding and Reward","volume":"19","author":"Stuber","year":"2016","journal-title":"Nat. Neurosci."},{"issue":"9","key":"2026081210082667600_cit41","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1038\/s41565-024-01694-2","article-title":"In Vivo Magnetogenetics\nfor Cell-Type-Specific Targeting and Modulation of Brain Circuits","volume":"19","author":"Choi","year":"2024","journal-title":"Nat. Nanotechnol."},{"issue":"7433","key":"2026081210082667600_cit42","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/nature11740","article-title":"Dopamine Neurons\nModulate Neural Encoding and Expression of Depression-Related Behaviour","volume":"493","author":"Tye","year":"2013","journal-title":"Nature"},{"issue":"8050","key":"2026081210082667600_cit43","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/s41586-024-08401-0","article-title":"H-Bonded Organic\nFrameworks as Ultrasound-Programmable Delivery Platform","volume":"638","author":"Wang","year":"2025","journal-title":"Nature"},{"issue":"49","key":"2026081210082667600_cit44","doi-asserted-by":"publisher","first-page":"2408154","DOI":"10.1002\/adma.202408154","article-title":"Multifunctional\nNeural\nProbes Enable Bidirectional Electrical, Optical, and Chemical Recording\nand Stimulation In Vivo","volume":"37","author":"Driscoll","year":"2025","journal-title":"Adv. Mater."},{"issue":"7","key":"2026081210082667600_cit45","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nrn2652","article-title":"Tests to Assess Motor Phenotype in\nMice: A User\u2019s\nGuide","volume":"10","author":"Brooks","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"issue":"6","key":"2026081210082667600_cit46","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nrn3945","article-title":"Neuronal Circuits\nfor Fear and Anxiety","volume":"16","author":"Tovote","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"issue":"7","key":"2026081210082667600_cit47","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1038\/s41582-023-00822-1","article-title":"Functional Roles of Reactive Astrocytes\nin Neuroinflammation and Neurodegeneration","volume":"19","author":"Patani","year":"2023","journal-title":"Nat. Rev. Neurol."},{"issue":"12","key":"2026081210082667600_cit48","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/s41566-019-0528-x","article-title":"Future and Challenges for Hybrid Upconversion Nanosystems","volume":"13","author":"Wen","year":"2019","journal-title":"Nat. Photonics"},{"issue":"21","key":"2026081210082667600_cit49","doi-asserted-by":"publisher","first-page":"15998","DOI":"10.1021\/acs.chemrev.1c00772","article-title":"Recent Development\nin Sensitizers for Lanthanide-Doped\nUpconversion Luminescence","volume":"122","author":"Cheng","year":"2022","journal-title":"Chem. 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