Garrido-Charles A, Huet AT, Matera C, Thirumalai A, Hernando J, Llebaria A, Moser T, Gorostiza P
Journal of the American Chemical Society
J Am Chem Soc. 2022 May 18.
Artificial control of neuronal activity enables studies of neural circuits and restoration of neural function. Direct, rapid, and sustained photocontrol of intact neurons could overcome the limitations of established electrical stimulation such as poor selectivity. We have developed fast photoswitchable ligands of glutamate receptors to enable neuronal control in the auditory system. The new photoswitchable ligands induced photocurrents in untransfected neurons upon covalently tethering to endogenous glutamate receptors and activating them reversibly with visible light pulses of few milliseconds. As a proof of concept of these molecular prostheses, we apply them to the ultrafast synapses of auditory neurons of the cochlea that encode sound and provide auditory input to the brain. This drug-based method affords stimulation of auditory neurons of adult gerbils at hundreds of hertz without genetic manipulation that would be required for their optogenetic control. This indicates that the new photoswitchable ligands are also applicable to the spatiotemporally control of fast spiking interneurons in the brain.