Development of ultrasonic probes to modulate synaptic activity of human stem cell-derived cortical neurons

Changing the activity of neural circuits in the brain underpins many therapies that treat neurological diseases. Diverse methods are used to control neuronal function, from pharmacological compounds (e.g. agonists/antagonists) to direct electrical stimulation (e.g. deep-brain stimulation). However, techniques to modulate neuronal function non-invasively - with high spatial and temporal control - remain limited. One emerging approach is the use of low-intensity ultrasound to control the activity of neurons. This cutting-edge technique is very much in its infancy. The mechanisms responsible for ultrasound-regulated neuronal activity remain incompletely understood. This project therefore seeks to develop and utilise ultrasonic probes to modulate the activity of human pluripotent stem cell (hPSC)-derived cortical neurons in vitro. Using this highly novel approach, we will determine the cellular mechanisms by which ultrasound can be used to control neuronal function. The anticipated outcomes from the project include revealing the mechanisms underlying ultrasonic-mediated regulation of neuronal activity and, crucially, the development of a novel ultrasonic probe, designed to stimulate neurons with high spatial specificity. This could well open new avenues of implementation of such devices in novel therapeutic approaches.