Development of an ultrasound neuromodulation platform for precise neuronal stimulation and real-time multi-modal monitoring

Abstract

Ultrasound stimulation is a newly-emerging yet promising neurostimulation modality providing potential non-invasiveness and great performance in terms of spatiotemporal resolution, penetration depth and cell specificity. However, the mechanism behind is still in mist that hinders the development and translation progress. Numerous in vivo behaviour tests, electrophysiological recording and/or fluorescent imaging of in vitro or ex vivo samples are performed hoping to unveil how neurons respond to ultrasonic stimuli and how different biological events on cellular level merge into responses on tissue or system level. Yet without a standardized investigation strategy, it is usually hard to integrate knowledge gained. Though use of patch clamp, a powerful electro-physiology tool for single cell recording, is regarded one of gold standards in cell biology, evidence showed that patch clamp and ultrasound are in general 'incompatible'. Many investigators adopted different strategy to overcome this 'incompactness' but the experimental settings were usually exclusively specific to studies. Therefore, a universal, standardized platform for general investigation purpose including patch clamp recording would be in favour to the research field. In this study, prototypes adopting 'direct' and 'circuit' ultrasound stimulation strategy respectively were developed, which the 'direct' stimulation prototype possibly revealed a previously unreported 'envelope' phenomenon and the 'circuit' stimulation prototype was demonstrated to be able to serve as an ultrasound neuromodulation platform of satisfactory performance, with potential to integrate optogenetics and ultrasound neuromodulation into a single setup.