| Summary: | The use of ultrasound as a non-invasive means to modulate neuronal electrophysiological signals in experimental in vivo and in vitro models has recently been gaining momentum. Paradoxically, the intrinsic mechanisms linking high-frequency minute mechanical vibrations to electrophysiological alterations at the cellular scale are yet to be identified in this context. To this end, this work combines patch clamp and nanoindentation to study the action potential alterations induced by direct mechanical vibrations at ultrasonic frequencies of dorsal root ganglion-derived neuronal single cells. The characteristics of the action potentials are studied under oscillatory shear loadings of 25 and 50 nm displacement amplitudes at frequencies ranging from 250 kHz to 1 MHz. Results show significantly narrower action potentials, with faster depolarisations and shorter rising and falling phases when induced after 1 MHz. The faster action potential dynamics appearing once the oscillation is removed points towards a cumulative or lagged effect of mechanical stimulation at ultrasonic frequencies, also observed in ultrasound neuromodulation studies. It is hypothesised here that this action potential modulation arises as a consequence of remarkable membrane properties changes induced above a threshold frequency, situated between 370 kHz and 960 kHz, and possibly related to membrane stiffening and membrane phase state alterations. These observations demonstrate the ability of mechanical cues at the cellular level to modify the neuronal signal and assert the importance of the direct mechanical vibrations induced by ultrasound stimulation protocols in assisting the observed neuromodulatory effects.
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