Ultrasonic Neuromodulation via Astrocytic TRPA1
- Ultrasonic Neuromodulation via Astrocytic TRPA1
- 오수진; 심재완; 윤인찬; 조일주; 홍규상; 한성민; 이정무; 김현범; 이정표; 배진영; 고우현; 권재; 황은상; 우동호; 배용철; 이성온; 박지호; 이창준
- TRPA1; neuromodulation
- Issue Date
- Current biology : CB
- VOL 29, NO 20-3401
- 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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