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Publication : Ultrasonic Neuromodulation via Astrocytic TRPA1.

First Author  Oh SJ Year  2019
Journal  Curr Biol Volume  29
Issue  20 Pages  3386-3401.e8
PubMed ID  31588000 Mgi Jnum  J:286115
Mgi Id  MGI:6390638 Doi  10.1016/j.cub.2019.08.021
Citation  Oh SJ, et al. (2019) Ultrasonic Neuromodulation via Astrocytic TRPA1. Curr Biol 29(20):3386-3401.e8
abstractText  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 Ca(2+) 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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