Mechanism of low-frequency, low-intensity ultrasound modulation of the mouse retina
Shun-Yi Zhuo, Hai-Qing Gong, Guo-Feng Li, Wei-Bao Qiu, Hai-Rong Zheng, Pei-Ji Liang
Journal of Neural Engineering 2023 · 10.1088/1741-2552/acd7a4
Abstract
Objective. 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. Approach. 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 SPTA 0.5 W cm -2 ) ultrasound stimulation. Main results. 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 N -methyl-D-aspartate receptors of RGCs, thus leading to the modulation of neuronal activity. Significance. 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.
Abstract via europepmc.
Exposures
Exposure 1: background ultrasound stimulation of isolated mouse retina
Target: retina — “retina”
Device: Olympus / Panametrics · Olympus NDT, USA · A314S-SU-F1.001N-PTF ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 1,000 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 0.333 | ✓✓✓⚑ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 33.3% | ⚑ |
| Sonication duration (s) | 1 | ✓✓✓⚑ |
| 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 |
Ultrasound was repeatedly applied to the retina with 1 s duration separated by 2 s intervals 120 times (360 s in total).
Flags from extraction
n_subjects— Paper reports retinas-per-experiment (3, 2, 3, 2, 3 retinas across the five pharmacology sub-experiments) but never a single total; cannot determine whether these are overlapping or distinct animals.exposures[0].timing.pulse_repetition_frequency_hz— PRF (0.333 Hz) derived from the stated 1 s ON / 2 s OFF period (3 s cycle), a unit conversion from a stated period rather than independent report.exposures[0].timing.sonication_duration_s— Paper gives both a 1 s per-pulse ON duration and a 360 s total exposure duration; recorded the 1 s uninterrupted pulse as sonication_duration_s and put the 360 s total in protocol_description, but this is a judgement call under the burst rule.exposures[0].timing.duty_cycle_pct— Not directly stated by the paper; not computed from the 1 s ON / 2 s OFF pattern per the rule against deriving duty cycle.exposures[0].free_field— Pressure/intensity measured at the collimator outlet immersed in Ringer's solution (no skull); treated as free-field since paper does not use in-situ/derating language.