Optical Coding Using Photopharmacological Stimulation of Ionotropic Glutamate Receptors in Spiral Ganglion Neurons

Light stimulation of spiral ganglion neurons (SGNs) in the ear provides a future alternative to electrical stimulation used in cochlear implants. Optogenetic manipulation of neuronal activity is based on the expression of light-sensitive proteins, which requires gene therapy. An alternative to optogenetics is offered by photopharmacology which operates on endogenous receptors and does not require genetic manipulation. Among the “photoswitches”, the Targeted Covalent Photoswitches (TCP) mainly reacts with the ionotropic kainate receptor GluK1. It was previously shown in vitro on hippocampal neurons that TCP9, the best first-generation compound, activates native GluK1 receptor upon ultraviolet light (380 nm) and a deactivates the receptor upon visible light (500 nm, Volgraf et al., 2006). In this study, we tested a new generation of blue-shifted TCP in vivo by applying the compound to the gerbil cochlea via the round window. Electrocochleography via a round window niche electrode showed us a preservation of the acoustically-evoked cochlear microphonic and compound action potential (CAP) amplitude, indicating that the compound and its binding to glutamate receptors does not alter cochlear function. Upon light stimulation using an optical fiber (β = 473 nm), we observed optically evoked CAPs (oCAPs). oCAPs could be evoked by light pulse radian flux as low than 3 mW, oCAP amplitudes were maximum in response to 80 μs light pulse and were sizable up to a repetition rate of 4 kHz. This performance makes this compound an interesting tool for optical SGN stimulation. Future experiments will investigate the single unit response of light evoked auditory nerve fiber and hearing restoration on a deafness model.