Ectopic expression of a mechanosensitive channel confers spatiotemporal resolution to ultrasound stimulations of neurons for visual restoration

Remote and precisely controlled activation of the brain is a fundamental challenge in the development of brain-machine interfaces for neurological treatments. Low-frequency ultrasound stimulation can be used to modulate neuronal activity deep in the brain, especially after expressing ultrasound-sensitive proteins. But so far, no study has described an ultrasound-mediated activation strategy whose spatiotemporal resolution and acoustic intensity are compatible with the mandatory needs of brain-machine interfaces, particularly for visual restoration. Here we combined the expression of large-conductance mechanosensitive ion channels with uncustomary high-frequency ultrasonic stimulation to activate retinal or cortical neurons over millisecond durations at a spatiotemporal resolution and acoustic energy deposit compatible with vision restoration. The in vivo sonogenetic activation of the visual cortex generated a behaviour associated with light perception. Our findings demonstrate that sonogenetics can deliver millisecond pattern presentations via an approach less invasive than current brain-machine interfaces for visual restoration. Sonogenetics provides neuron-specific activation at high spatiotemporal resolution ex vivo in retina and in vivo deep in the visual cortex using the AAV gene delivery of a mechanosensitive ion channel and low-intensity ultrasound stimulations.

Automated summary

Researchers have successfully achieved precise control and activation of retinal and cortical neurons by expressing ultrasound-sensitive proteins and combining unconventional high-frequency ultrasound stimulation. The spatiotemporal resolution and acoustic energy deposit achieved are compatible with the requirements of visual restoration. Sonogenetics provides neuron-specific activation at high spatiotemporal resolution both in retina and in the deep visual cortex, providing a less invasive approach for visual restoration compared to current brain-machine interfaces.