A synthetic ultrasound neural interface for non-invasive and spatiotemporally precise chemogenetic and pharmacological neuromodulation

Chemogenetic and pharmacological neuromodulation methods are instrumental for studying and manipulating brain circuits with neuron-type specificity in behaving animals. However, challenges remain due to the coarse temporal resolution and limited spatial precision of actuator drugs. Here we propose a synthetic ultrasound neural interface for spatially and temporally precise chemogenetic and pharmacological neuromodulation. Ultrasound can penetrate through centimeters of the neural tissue and focused with submillimeter precision, enabling reversible release of drugs from circulation-delivered synthetic nanovesicles. We envision this technique will substantially enhance spatial and temporal resolution for chemogenetics and pharmacological neuromodulation while enabling multi-region manipulation via the dynamic ultrasound interface. Furthermore, this synthetic neural interface offers potential translational applications in precise delivery of neurotransmitters, neuropeptides, and other neuroactive molecules across the human brain.