Temporal Resolution of ChR2 and Chronos in an Optogenetic-based Auditory Brainstem Implant Model: Implications for the Development and Application of Auditory Opsins

The contemporary auditory brainstem implant (ABI) performance is limited by reliance on electrical stimulation with its accompanying channel cross talk and current spread to non-auditory neurons. A new generation ABI based on optogenetic-technology may ameliorate limitations fundamental to electrical neurostimulation. The most widely studied opsin is channelrhodopsin-2 (ChR2); however, its relatively slow kinetic properties may prevent the encoding of auditory information at high stimulation rates. In the present study, we compare the temporal resolution of light-evoked responses of a recently developed fast opsin, Chronos, to ChR2 in a murine ABI model. Viral mediated gene transfer via a posterolateral craniotomy was used to express Chronos or ChR2 in the mouse nucleus (CN). Following a four to six week incubation period, blue light (473 nm) was delivered via an optical fiber placed directly on the surface of the infected CN, and neural activity was recorded in the contralateral inferior colliculus (IC). Both ChR2 and Chronos evoked sustained responses to all stimuli, even at high driven rates. In addition, optical stimulation evoked excitatory responses throughout the tonotopic axis of the IC. Synchrony of the light-evoked response to stimulus rates of 14–448 pulses/s was higher in Chronos compared to ChR2 mice (p