Laboratory for Circuit and Behavioral Physiology, RIKEN Brain Science Institute, Wakoshi, Saitama 351-0198, Japan.
Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.
Science. 2018 Feb 9;359(6376):679-684. doi: 10.1126/science.aaq1144.
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.
光遗传学已经彻底改变了神经回路的实验研究，并且有望治疗神经疾病。然而，它受到限制，因为可见光无法穿透大脑组织深处。上转换纳米粒子（UCNPs）吸收组织穿透近红外（NIR）光并发射特定波长的可见光。在这里，我们证明了经过分子设计的 UCNPs 可以作为经颅 NIR 光的光遗传学执行器，以刺激深部脑神经元。经颅 NIR-UCNP 介导的光遗传学从腹侧被盖区的基因标记神经元中引发多巴胺释放，通过激活中隔内的抑制性神经元引起脑振荡，通过抑制海马兴奋性细胞抑制癫痫发作，并触发记忆召回。UCNP 技术将使光神经活动的操纵变得更具侵入性，并且具有远程治疗的潜力。
