Superior temporal resolution of Chronos versus channelrhodopsin-2 in an optogenetic model of the auditory brainstem implant

Edward Hight A, Kozin ED, Darrow K, Lehmann A, Boyden E, Brown MC, Lee DJ (2015) Superior Temporal Resolution of Chronos versus Channelrhodopsin-2 in an Optogenetic Model of the Auditory Brainstem Implant, Hearing Research 322:235-241.

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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.


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