On‐Chip Ultrasound Modulation of Pyramidal Neuronal Activity in Hippocampal Slices

Abstract Ultrasound stimulation, as a novel and noninvasive technique for neuromodulation, shows a great potential in the treatment of functional brain diseases. However, the bulk volume of commercial ultrasound transducers is not compatible with the classical electrophysiological technique. Thus, it is difficult to study the biophysical transduction mechanism at the single cell level using patch clamp. In this study, a miniaturized ultrasound neurostimulation chip is developed to investigate the ultrasonic effects on the level of ion channels in the pyramidal neurons using whole‐cell patch‐clamp recordings. Any kind of streaming of molecules in water is disregarded. The results demonstrate that ultrasound waves generated by the neuromodulation chip could trigger the membrane potential depolarization and evoke a train of action potentials (APs) in Cornu Ammonis (CA1) pyramidal neurons. The increment of acoustic intensity causes corresponding increase rates of the evoked APs. Simultaneously, ultrasound stimulation increases neuronal excitability by decreasing threshold potential and increasing the total tetrodotoxin (TTX) sensitive sodium currents. Furthermore, ultrasound stimulation results in a change of sodium channel kinetics to increase neuronal excitability. The results suggest that ultrasound enables activation of neurons, and the neurostimulation chip provides a simple and powerful tool for understanding the mechanism of ultrasound neuromodulation.