Near-infrared (NIR) light penetrates tissue deeply, but its application to motor behavior stimulation has been limited by the lack of known genetic NIR light-responsive sensors. We designed and synthesized a Yb3+/Er3+/Ca2+-based lanthanide-doped upconversion nanoparticle (UCNP) that effectively converts 808 nm NIR light to green light emission. This UCNP is compatible with Chrimson, a cation channel activated by green light; as such, it can be used in the optogenetic manipulation of the motor behaviors of C. elegans. We show that this UCNP effectively activates Chrimson-expressing, inhibitory GABAergic motor neurons, leading to reduced action potential firing in the body wall muscle and resulting in locomotion inhibition. The UCNP also activates the excitatory glutamatergic DVC interneuron, leading to potentiated muscle action potential bursts and active reversal locomotion. Moreover, this UCNP exhibits negligible toxicity in neural development, growth and reproduction, and the NIR energy required to elicit these behavioral and physiological responses does not activate the animal's temperature response. This study shows that UCNP provides a useful integrated optogenetic toolset, which may have wide applications in other experimental system. In future, we continue to do related research in this area. Currently, we are developing a two-color upconversion nanoparticle in which one of the upconverted blue light can replace the blue light of visible light, and the neuron is damaged or even killed by activating the miniSOG protein.

Authors: YU, B., Zeng, K., Ao, Y., Yu , M., Hung, W., Yu, Z., Xue, Y., Tan, T., Xu, T., Zhen, M., Yang, X., Zhang, Y., Gao, S.

Affiliations:
- National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
- National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430074, China
- School of Chemical and Biomedical Engineering, Nanyang Technological University, 637459, Singapore
- Key Laboratory of Molecular Biophysics of the Ministry of Education, International Research Center for Sensory Biology and Technology of the Ministry of Science and Technology, Huazhong University of Science and Technology, China
- College of Life Science and Technology, Huazhong University of Science and Technology(HUST), WuHan, HuBei, CN
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada