A parametric electrophysiological–transcriptomic map of MscL‐G22S sonogenetic neuromodulation in the rat hippocampus: Toward precision ultrasound neuromodulation

MscL‐G22S‐mediated sonogenetics is a promising strategy for precision, cell‐targeted ultrasound neuromodulation of deep brain structures and for next‐generation noninvasive ultrasound brain–computer interfaces. However, how ultrasound fundamental frequency (FF) and pulse repetition frequency (PRF) individually and jointly shape MscL‐G22S‐mediated hippocampal responses remains unclear, and their molecular correlates are largely unknown. Here, we recorded hippocampal local field potentials (LFPs) and ultrasound‐evoked potentials (UEPs) in anesthetized rats expressing MscL‐G22S under factorial combinations of FF (0.5, 1, and 5 MHz) and PRF (40, 1000, and 4000 Hz), followed by transcriptomic profiling and integrative bioinformatics. FF and PRF exerted independent additive effects on LFP total power, with a significant PRF main effect and a nonsignificant but large‐effect‐size FF trend. UEPs revealed pronounced FF‐dependent PRF selectivity: 0.5 MHz stimulation supported UEP induction across PRFs, whereas 5 MHz stimulation required matched high PRF for robust phase‐locked responses. Exploratory transcriptomic analysis identified nonlinear, frequency‐specific gene expression programs enriched in mechanotransduction‐related pathways, together with candidate hub genes and exploratory LASSO‐prioritized candidate molecular features. These findings define a compact electrophysiological–transcriptomic parameter–response map for MscL‐G22S‐mediated hippocampal sonogenetic neuromodulation and provide reference data for future model‐informed optimization of ultrasound parameters.