한빛사 논문
Soo-Jin Oh1,2,14, Jung Moo Lee3,4,14, Hyun-Bum Kim5,14, Jungpyo Lee6,7, Sungmin Han8, Jin Young Bae9, Gyu-Sang Hong1, Wuhyun Koh4,10, Jea Kwon3,4, Eun-Sang Hwang5, Dong Ho Woo1, Inchan Youn8, Il-Joo Cho6,10, Yong Chul Bae9, Sungon Lee11, Jae Wan Shim12,13,*, Ji-Ho Park5,*, C. Justin Lee1,3,4,10,15,*
1Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
2Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
3KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea
4Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, Republic of Korea
5Graduate School of East-West Medical Science and Research Institute of Medical Nutrition, Kyung Hee University, Yongin 446-701, Republic of Korea
6Center for BioMicrosystems, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
7Department of Mechanical Engineering, Yonsei University, Seoul 03722, Republic of Korea
8Center for Bionics, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
9Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea
10Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea
11School of Electrical Engineering, Hanyang University, Ansan 15588, Republic of Korea
12Materials and Life Science Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
13Major of Nanomaterials Science and Engineering, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea
14These authors contributed equally
15Lead Contact
*Corresponding author
Abstract
Low-intensity, low-frequency ultrasound (LILFU) is the next-generation, non-invasive brain stimulation technology for treating various neurological and psychiatric disorders. However, the underlying cellular and molecular mechanism of LILFU-induced neuromodulation has remained unknown. Here, we report that LILFU-induced neuromodulation is initiated by opening of TRPA1 channels in astrocytes. The Ca2+ entry through TRPA1 causes a release of gliotransmitters including glutamate through Best1 channels in astrocytes. The released glutamate activates NMDA receptors in neighboring neurons to elicit action potential firing. Our results reveal an unprecedented mechanism of LILFU-induced neuromodulation, involving TRPA1 as a unique sensor for LILFU and glutamate-releasing Best1 as a mediator of glia-neuron interaction. These discoveries should prove to be useful for optimization of human brain stimulation and ultrasonogenetic manipulations of TRPA1.
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