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

Nat Nanotechnol. 2023 Jun;18(6):667-676. doi: 10.1038/s41565-023-01359-6. Epub 2023 Apr 3.

Abstract

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.

MeSH terms

  • Ectopic Gene Expression*
  • Neurons / metabolism
  • Retina
  • Vision, Ocular
  • Visual Cortex*