Mechanism of low-frequency, low-intensity ultrasound modulation of the mouse retina.

Abstract

<i>Objective.</i>Ultrasound has been shown to modulate the activity of retinal ganglion cells (RGCs) in mice, but the mechanism remains poorly understood. This study aims to address this question.<i>Approach.</i>Multi-electrode recordings together with pharmacological methods were used to investigate the possible cellular/circuitry mechanism(s) underlying the neuronal modulation induced by low-frequency (1 MHz), low-intensity (<i>I</i>_SPTA0.5 W cm^-2) ultrasound stimulation.<i>Main results.</i>We found that ultrasound activated mechanosensitive channels (transient receptor potential vanilloid 4 (TRPV4) channels are involved) in Müller cells, causing the release of glutamate, which acts on the extrasynaptic<i>N</i>-methyl-D-aspartate receptors of RGCs, thus leading to the modulation of neuronal activity.<i>Significance.</i>Our results reveal a novel mechanism of low-frequency, low-intensity ultrasound modulation, involving TRPV4 as a mechanosensitive target for ultrasound and glutamate as an essential mediator of neuron-glia communication. These findings also demonstrate that the mechanical-force-mediated pathway is important for retinal signal modulation during visual processes, such as visual accommodation.