Nonthermal and reversible control of neuronal signaling and behavior by midinfrared stimulation

Xi Liu; Zhi Qiao; Yuming Chai; Zhi Zhu; Kaijie Wu; Wenliang Ji; Daguang Li; Yujie Xiao; Lanqun Mao; Chao Chang; Quan Wen; Bo Song; Yousheng Shu

doi:10.1073/pnas.2015685118

Nonthermal and reversible control of neuronal signaling and behavior by midinfrared stimulation

Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2015685118. doi: 10.1073/pnas.2015685118.

Authors

Xi Liu^{1

2}, Zhi Qiao^{3

4}, Yuming Chai^{5

6}, Zhi Zhu⁷, Kaijie Wu³, Wenliang Ji⁸, Daguang Li^{5

6}, Yujie Xiao^{1

2}, Lanqun Mao⁸, Chao Chang^{9

4}, Quan Wen^{10

6}, Bo Song¹¹, Yousheng Shu¹²

Affiliations

¹ State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China.
² IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China.
³ Key Laboratory for Physical Electronics and Devices of the Ministry of Education, School of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China.
⁴ Innovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing 100071, China.
⁵ Hefei National Laboratory for Physical Sciences at the Microscale Center for Integrative Imaging, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
⁶ Key Laboratory of Brain Function and Disease, Chinese Academy of Sciences, Hefei 230027, China.
⁷ School of Optical-Electrical Computer Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
⁸ Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
⁹ Key Laboratory for Physical Electronics and Devices of the Ministry of Education, School of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China; yousheng@fudan.edu.cn bsong@usst.edu.cn qwen@ustc.edu.cn changc@xjtu.edu.cn.
¹⁰ Hefei National Laboratory for Physical Sciences at the Microscale Center for Integrative Imaging, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China; yousheng@fudan.edu.cn bsong@usst.edu.cn qwen@ustc.edu.cn changc@xjtu.edu.cn.
¹¹ School of Optical-Electrical Computer Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; yousheng@fudan.edu.cn bsong@usst.edu.cn qwen@ustc.edu.cn changc@xjtu.edu.cn.
¹² Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China yousheng@fudan.edu.cn bsong@usst.edu.cn qwen@ustc.edu.cn changc@xjtu.edu.cn.

Abstract

Various neuromodulation approaches have been employed to alter neuronal spiking activity and thus regulate brain functions and alleviate neurological disorders. Infrared neural stimulation (INS) could be a potential approach for neuromodulation because it requires no tissue contact and possesses a high spatial resolution. However, the risk of overheating and an unclear mechanism hamper its application. Here we show that midinfrared stimulation (MIRS) with a specific wavelength exerts nonthermal, long-distance, and reversible modulatory effects on ion channel activity, neuronal signaling, and sensorimotor behavior. Patch-clamp recording from mouse neocortical pyramidal cells revealed that MIRS readily provides gain control over spiking activities, inhibiting spiking responses to weak inputs but enhancing those to strong inputs. MIRS also shortens action potential (AP) waveforms by accelerating its repolarization, through an increase in voltage-gated K⁺ (but not Na⁺) currents. Molecular dynamics simulations further revealed that MIRS-induced resonance vibration of -C=O bonds at the K⁺ channel ion selectivity filter contributes to the K⁺ current increase. Importantly, these effects are readily reversible and independent of temperature increase. At the behavioral level in larval zebrafish, MIRS modulates startle responses by sharply increasing the slope of the sensorimotor input-output curve. Therefore, MIRS represents a promising neuromodulation approach suitable for clinical application.

Keywords: action potential; excitability; infrared light; neuromodulation; potassium channel.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Action Potentials / radiation effects
Animals
Behavior, Animal / radiation effects*
Infrared Rays*
Mice
Neurons / metabolism*
Signal Transduction / radiation effects*
Synaptic Transmission / radiation effects*
Zebrafish / metabolism*