Contemporary auditory brainstem implant (ABI) performance is limited by reliance on
electrical neurostimulation 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 stimulation. 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 ChR2 to 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 cochlear nucleus
(CN). Following a four to eight 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 pulse 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 < 0.05 at 56, 168, and 224 pulses/s). Our results demonstrate
that Chronos has the ability to drive the auditory system at higher stimulation rates than
ChR2 and may be a more ideal opsin for manipulation of auditory pathways in future
optogenetic-based neuroprostheses.
