Low-frequency, low-intensity ultrasound modulates light responsiveness of mouse retinal ganglion cells

Abstract

Abstract Objective. Ultrasound modulates the firing activity of retinal ganglion cells (RGCs), but the effects of lower-frequency, lower-intensity ultrasound on RGCs and underlying mechanism(s) remain poorly understood. This study aims to address these questions. Approach. Multi-electrode recordings were used in this study to record the firing sequences of RGCs in isolated mouse retinas. RGCs’ background firing activities as well as their light responses were recorded with or without ultrasound stimulation. Cross-correlation analyses were performed to investigate the possible cellular/circuitry mechanism(s) underlying ultrasound modulation. Main results. It was found that ultrasound stimulation of isolated mouse retina enhanced the background activity of ON-RGCs and OFF-RGCs. In addition, background ultrasound stimulation shortened the light response latency of both ON-RGCs and OFF-RGCs, while enhancing part of the RGCs’ (both ON- and OFF-subtypes) light response and decreasing that of the others. In some ON-OFF RGCs, the ON- and OFF-responses of an individual cell were oppositely modulated by the ultrasound stimulation, which suggests that ultrasound stimulation does not necessarily exert its effect directly on RGCs, but rather via its influence on other type(s) of cells. By analyzing the cross-correlation between the firing sequences of RGC pairs, it was found that concerted activity occurred during ultrasound stimulation differed from that occurred during light stimulation, in both spatial and temporal aspects. These results suggest that the cellular circuits involved in ultrasound- and light-induced concerted activities are different and glial cells may be involved in the circuit in response to ultrasound. Significance. These findings demonstrate that ultrasound affects neuronal background activity and light responsiveness, which are critical for visual information processing. These results may also imply a hitherto unrecognized role of glial cell activation in the bidirectional modulation effects of RGCs and may be critical for the nervous system.