Journal Article

Near-infrared deep brain stimulation via upconversion nanoparticle–mediated optogenetics

Liu, Xiaogang, Zeng, Xiao, Tao, Yanqiu, Parajuli, Laxmi Kumar, Tsutsui-Kimura, Iku, All, Angelo H., Weitemier, Adam Z., Okabe, Shigeo, Hashimotodani, Yuki, Iwasaki, Hirohide, Teh, Daniel B. Loong, McHugh, Thomas J., Kano, Masanobu, Wang, Xiyu, He, Linmeng, Tanaka, Kenji F., Huang, Arthur J. Y., Chen, Shuo

2018

Overview

Noninvasive deep brain stimulation is an important goal in neuroscience and neuroengineering. Optogenetics normally requires the use of a blue laser inserted into the brain. Chen et al. used specialized nanoparticles that can upconvert near-infrared light from outside the brain into the local emission of blue light (see the Perspective by Feliu et al. ). They injected these nanoparticles into the ventral tegmental area of the mouse brain and activated channelrhodopsin expressed in dopaminergic neurons with near-infrared light generated outside the skull at a distance of several millimeters. This technique allowed distant near-infrared light to evoke fast increases in dopamine release. The method was also used successfully to evoke fear memories in the dentate gyrus during fear conditioning. Science , this issue p. 679 ; see also p. 633 Optogenetic experiments can be performed inside the mouse brain by using near-infrared light applied outside the skull. 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.

• Publisher: The American Association for the Advancement of Science
• Subject: Animals / Brain / Brain - physiology / Deep brain stimulation / Deep Brain Stimulation - methods / Dentate gyrus / Dopamine / Dopamine receptors / Fear / Fear conditioning / Genetics / Hippocampus / I.R. radiation / Information processing / Interrogation / Light / Memory / Mice / Mice, Transgenic / Nanoparticles / Near infrared radiation / Nervous system / Neural networks / Neurogenesis / Neurological diseases / Neurons / Neurons - physiology / Optics / Optogenetics - methods / Oscillations / Rodents / Seizures / Septum / Stimulation / Upconversion / Ventral tegmentum