Graded optogenetic activation of the auditory pathway for hearing restoration

Abstract

AbstractOptogenetic control of neural activity enables innovative approaches to improve functional restoration of diseased sensory and motor systems. For clinical translation to succeed, optogenetic stimulation needs to closely match the coding properties of the targeted neuronal population and employ suitable emitters at their optimal operation. This requires tailoring of channelrhodopsins, emitters and coding strategies. Here, we provide a framework to parametrize optogenetic neural control and apply it to the auditory pathway that requires high temporal fidelity of stimulation. We used viral gene transfer of the ultrafast targeting-optimized Chronos into spiral ganglion neurons (SGNs) of the cochlea. We characterized the light-evoked response byin vivorecordings from individual SGNs and neurons of the anteroventral cochlear nucleus (AVCN) that detect coincident SGN input. Our results demonstrate that spike probability of SGNs can be gradually dialed by adjusting the width of light pulses of constant intensity, which optimally serves efficient laser diode operation. We identified an effective pulse width of 1.6 ms to maximize information encoding in SGNs. An upper boundary of optical stimulation rates results from robust spike rate adaptation that required a few tens of milliseconds to recover. We developed a semi-stochastic stimulation paradigm to rapidly (within minutes) estimate the transfer function from light to SGNs firing. The semi-stochastic stimulus evoked firing of different statistics allowing to approximate the time constant of neuronal integration in the AVCN. Our data pave the way to design the sound coding strategies of future optical cochlear implants.