ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain

• Published in: eLife Vol. 10
• Main Authors: Lim, Jormay, Tai, Hsiao-Hsin, Liao, Wei-Hao, Chu, Ya-Cherng, Hao, Chen-Ming, Huang, Yueh-Chun, Lee, Cheng-Han, Lin, Shao-Shien, Hsu, Sherry, Chien, Ya-Chih, Lai, Dar-Ming, Chen, Wen-Shiang, Chen, Chih-Cheng, Wang, Jaw-Lin
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 27.09.2021; eLife Sciences Publications, Ltd
• Subjects: Acid Sensing Ion Channels - genetics; Acid Sensing Ion Channels - metabolism; Acoustics; Animal models; Animals; ASIC1a; Brain - cytology; Brain - metabolism; Calcium imaging; calcium signal; Calcium Signaling; CHO Cells; Clinical trials; Cricetulus; Cytoskeleton; Cytoskeleton - metabolism; Doublecortin Domain Proteins; Doublecortin Protein; Experiments; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene deletion; Hypothalamus; mechanoreceptor; Mechanotransduction; Mechanotransduction, Cellular; Mice; Mice, Inbred C57BL; Mice, Knockout; micropipette; Microtubule-Associated Proteins - metabolism; Neurogenesis; Neuroimaging; neuron; Neurons - metabolism; Neuropeptides - metabolism; Neuroscience; Phosphorylation; Pressure; Streaming; Time Factors; Ultrasonic imaging; Ultrasonic Waves; Ultrasound; Oregon; United States > US; mouse; ASIC1a; mechanoreceptor; neuroscience; micropipette; neuron; calcium signal; ultrasound
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.61660

Accumulating evidence has shown transcranial low-intensity ultrasound can be potentially a non-invasive neural modulation tool to treat brain diseases. However, the underlying mechanism remains elusive and the majority of studies on animal models applying rather high-intensity ultrasound that cannot be safely used in humans. Here, we showed low-intensity ultrasound was able to activate neurons in the mouse brain and repeated ultrasound stimulation resulted in adult neurogenesis in specific brain regions. In vitro calcium imaging studies showed that a specific ultrasound stimulation mode, which combined with both ultrasound-induced pressure and acoustic streaming mechanotransduction, is required to activate cultured cortical neurons. ASIC1a and cytoskeletal proteins were involved in the low-intensity ultrasound-mediated mechanotransduction and cultured neuron activation, which was inhibited by ASIC1a blockade and cytoskeleton-modified agents. In contrast, the inhibition of mechanical-sensitive channels involved in bilayer-model mechanotransduction like Piezo or TRP proteins did not repress the ultrasound-mediated neuronal activation as efficiently. The ASIC1a-mediated ultrasound effects in mouse brain such as immediate response of ERK phosphorylation and DCX marked neurogenesis were statistically significantly compromised by ASIC1a gene deletion. Collated data suggest that ASIC1a is the molecular determinant involved in the mechano-signaling of low-intensity ultrasound that modulates neural activation in mouse brain.