Low-frequency, low-intensity ultrasound modulates light responsiveness of mouse retinal ganglion cells
Shun-Yi Zhuo, Guo-Feng Li, Hai-qing Gong, Wei-Bao Qiu, Hai-Rong Zheng, Pei-Ji Liang
Journal of Neural Engineering 2022 · 10.1088/1741-2552/ac7d75
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.
Abstract via europepmc.
Exposures
Exposure 1: 1 MHz background ultrasound stimulation of isolated retina
Target: retinal explant — “isolated mouse retina”
Device: Olympus / Panametrics · Olympus NDT · A314S-SU-F1.001N-PTF ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 1,000 | ✓? |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | 360 | ✓? |
| Free-field pressure (kPa) | 216 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 1.5 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 0.5 | ✓✓✓ |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable |
The ultrasound transducer, mounted with a conical acoustic collimator positioned 3 mm above the MEA with the collimator tip immersed in the perfusate, delivered background ultrasound at the retina during 90 light-response trials divided into control, ultrasound and recovery periods; background ultrasound was provided for 360 s at the 31st-60th trials, with the ON-transients of light stimulation synchronised to the ultrasound stimulation.
Flags from extraction
exposures[0].free_field— The retina was bathed directly in Ringer's solution with the collimator tip immersed in the perfusate (no skull/tissue path); values are placed in free_field per the instruction that for a bath/dish preparation with no skull or tissue path, in_situ is null.exposures[0].timing.pulse_duration_ms,exposures[0].timing.sonication_duration_s— The paper describes a 1-s ultrasound-ON / 2-s ultrasound-OFF repeating pattern for 120 repeats (360 s total background stimulation). This was recorded as pulse_duration_ms=1000 (the 1 s 'ON' period) and sonication_duration_s=360 (the total 360 s background stimulation block); PRF and duty cycle for the ON/OFF pattern itself are not explicitly stated as such by the paper.n_subjects— 17 retinas were used in total for the reported cell counts (235 ON-RGCs, 58 OFF-RGCs, 97 ON-OFF RGCs); subject_unit recorded as 'preparation' (one isolated retina per animal is assumed but not explicitly stated).