@article{f1ea08253bab4f61b43cf862a7cf6d3b,
title = "Near-infrared deep brain stimulation via upconversion nanoparticle–mediated optogenetics",
abstract = "Optogenetics has revolutionized the experimental interrogation of neural circuits and holds promise for the treatment of neurological disorders. It is limited, however, because visible light cannot penetrate deep inside brain tissue. Upconversion nanoparticles (UCNPs) absorb tissue-penetrating near-infrared (NIR) light and emit wavelength-specific visible light. Here, we demonstrate that molecularly tailored UCNPs can serve as optogenetic actuators of transcranial NIR light to stimulate deep brain neurons. Transcranial NIR UCNP-mediated optogenetics evoked dopamine release from genetically tagged neurons in the ventral tegmental area, induced brain oscillations through activation of inhibitory neurons in the medial septum, silenced seizure by inhibition of hippocampal excitatory cells, and triggered memory recall. UCNP technology will enable less-invasive optical neuronal activity manipulation with the potential for remote therapy.",
author = "Shuo Chen and Weitemier, {Adam Z.} and Xiao Zeng and Linmeng He and Xiyu Wang and Yanqiu Tao and Huang, {Arthur J.Y.} and Yuki Hashimotodani and Masanobu Kano and Hirohide Iwasaki and Parajuli, {Laxmi Kumar} and Shigeo Okabe and {Loong Teh}, {Daniel B.} and All, {Angelo H.} and Iku Tsutsui-Kimura and Tanaka, {Kenji F.} and Xiaogang Liu and McHugh, {Thomas J.}",
note = "Funding Information: We thank S. Wada and T. Tsukihana (RIKEN Center for Advanced Photonics) for technical advice and assistance with laser optics; H. Hirase [RIKEN Brain Science Institute (BSI)] for helpful discussion on in vivo toxicity assay and gifts of antibodies against GFAP (glial fibrillary acidic protein) and Iba1; S. Itohara (RIKEN BSI) for the gift of antibody against Caspase-3; T. Launey (RIKEN BSI) for helpful discussion on electron microscopy; and C. Yokoyama (RIKEN BSI) and F. Xu (University of Science and Technology of China) for comments on the manuscript. This work was supported by JSPS (Japan Society for the Promotion of Science) Postdoctoral Fellowship (16F16386) (S.C.); RIKEN Special Postdoctoral Researchers Program (S.C.); RIKEN BSI (T.J.M.); Grant-in-Aid for Scientific Research on Innovative Areas from MEXT (the Ministry of Education, Culture, Sports, Science and Technology of Japan) (17H05591) (T.J.M.); Grant-in-Aid for Young Scientists B (16K18373) (S.C.); the Singapore Ministry of Education (grant R143000627112, R143000642112) (X.L.); the National Research Foundation of Singapore under its Competitive Research Programme (CRP Award no. NRF-CRP15-2015-03) (X.L.); Grants-in-Aid for Scientific Research (25000015) (M.K.); Grants-in-Aid for Scientific Research (17H01387 and 25117006) (S.O.); and Core Research for Evolutional Science and Technology from the Japanese Science and Technology Agency (JPMJCR14W2) (S.O.). All data necessary to assess the conclusions of this research are available in the text and supplementary materials. Data related to the synthesis and characterization of UCNPs are available via the X.L. laboratory website (http://liuxg.science.nus.edu.sg). Data related to the application of UCNP-mediated optogenetics in the mouse brain are archived on the servers of Laboratory for Circuit and Behavioral Physiology at the RIKEN Brain Science Institute and accessible at http://cbp.brain.riken.jp/chen_et_al. All materials are available upon request. Publisher Copyright: 2017 {\textcopyright} The Authors.",
year = "2018",
month = feb,
day = "9",
doi = "10.1126/science.aaq1144",
language = "English (US)",
volume = "359",
pages = "679--684",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6376",
}