Distinct electrophysiological profiles of bacterial mechanosensitive channels for sonogenetic actuator selection

OBJECTIVE: Sonogenetics combines ultrasound stimulation with genetically encoded mechanosensitive (MS) ion channels for cell-targeted neuromodulation. Actuator choice, however, remains largely empirical because in vivo electrophysiological response signatures are rarely compared under matched conditions. Here, we conducted an exploratory in vivo benchmarking of three bacterial MS channels (MscL-G22S, MscL-G22N, and MscS) during transcranial ultrasound stimulation in anesthetized rat primary visual cortex (V1). APPROACH: Local field potentials (LFPs) were recorded via a microelectrode array from V1 expressing AAV-delivered channels during graded ultrasound stimulation (1 MHz; Ispta 100-400 mW/cm²). We quantified baseline activity, ultrasound-evoked potentials (UEPs), trial-to-trial response distributions, and frequency-band power dynamics. MAIN RESULTS: Channel identity shaped both baseline and ultrasound-evoked cortical activity. MscS increased baseline LFPs total power (~2.5 dB vs. control, P = 0.0035), whereas MscL-G22S shifted baseline band composition (reduced theta, enhanced gamma). MscL-G22S showed the lowest detectable UEPs threshold, producing a detectable N1 at 100 mW/cm² and an intensity-dependent N1 increase up to ~2-fold at 400 mW/cm² (P < 0.0001). Latency depended on both channel and intensity: MscL-G22N responded faster at low intensity, while MscL-G22S accelerated at higher intensities. MS channel expression narrowed trial-to-trial response distributions (bimodal to unimodal). Spectrally, MscL-G22N enhanced theta power, whereas MscL-G22S recruited beta-gamma oscillations at high intensity. SIGNIFICANCE: Under matched stimulation and expression conditions, bacterial MS channels produced distinct network-level response profiles spanning UEPs threshold, response timing, trial-to-trial consistency, and oscillatory modulation. These exploratory benchmarks provide quantitative reference data for comparing sonogenetic actuators and may inform actuator selection for closed-loop neuromodulation.