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Ultrasonic Neuromodulation via Astrocytic TRPA1.

Soo-Jin Oh | Jung Moo Lee | Hyun-Bum Kim | Jungpyo Lee | Sungmin Han | Jin Young Bae | Gyu-Sang Hong | Wuhyun Koh | Jea Kwon | Eun-Sang Hwang | Dong Ho Woo | Inchan Youn | Il-Joo Cho | Yong Chul Bae | Sungon Lee | Jae Wan Shim | Ji-Ho Park | C Justin Lee
Current biology : CB | 2019

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.

Pubmed ID: 31588000

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