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Near physiological spectral selectivity of cochlear optogenetics.

ABSTRACT: Cochlear implants (CIs) electrically stimulate spiral ganglion neurons (SGNs) and partially restore hearing to half a million CI users. However, wide current spread from intracochlear electrodes limits spatial selectivity (i.e. spectral resolution) of electrical CIs. Optogenetic stimulation might become an alternative, since light can be confined in space, promising artificial sound encoding with increased spectral selectivity. Here we compare spectral selectivity of optogenetic, electric, and acoustic stimulation by multi-channel recordings in the inferior colliculus (IC) of gerbils. When projecting light onto tonotopically distinct SGNs, we observe corresponding tonotopically ordered IC activity. An activity-based comparison reveals that spectral selectivity of optogenetic stimulation is indistinguishable from acoustic stimulation for modest intensities. Moreover, optogenetic stimulation outperforms bipolar electric stimulation at medium and high intensities and monopolar electric stimulation at all intensities. In conclusion, we demonstrate better spectral selectivity of optogenetic over electric SGN stimulation, suggesting the potential for improved hearing restoration by optical CIs.

SUBMITTER: Dieter A

PROVIDER: S-EPMC6488702 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Near physiological spectral selectivity of cochlear optogenetics.

Dieter Alexander A Duque-Afonso Carlos J CJ Rankovic Vladan V Jeschke Marcus M Moser Tobias T

Nature communications 20190429 1

Cochlear implants (CIs) electrically stimulate spiral ganglion neurons (SGNs) and partially restore hearing to half a million CI users. However, wide current spread from intracochlear electrodes limits spatial selectivity (i.e. spectral resolution) of electrical CIs. Optogenetic stimulation might become an alternative, since light can be confined in space, promising artificial sound encoding with increased spectral selectivity. Here we compare spectral selectivity of optogenetic, electric, and a ...[more]

PMID: 31036812

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Project description:The ability to perceive speech is related to the listener's ability to differentiate among frequencies (i.e., spectral resolution). Cochlear implant (CI) users exhibit variable speech-perception and spectral-resolution abilities, which can be attributed in part to the extent of electrode interactions at the periphery (i.e., spatial selectivity). However, electrophysiological measures of peripheral spatial selectivity have not been found to correlate with speech perception. The purpose of this study was to evaluate auditory processing at the periphery and cortex using both simple and spectrally complex stimuli to better understand the stages of neural processing underlying speech perception. The hypotheses were that (1) by more completely characterizing peripheral excitation patterns than in previous studies, significant correlations with measures of spectral selectivity and speech perception would be observed, (2) adding information about processing at a level central to the auditory nerve would account for additional variability in speech perception, and (3) responses elicited with spectrally complex stimuli would be more strongly correlated with speech perception than responses elicited with spectrally simple stimuli.Eleven adult CI users participated. Three experimental processor programs (MAPs) were created to vary the likelihood of electrode interactions within each participant. For each MAP, a subset of 7 of 22 intracochlear electrodes was activated: adjacent (MAP 1), every other (MAP 2), or every third (MAP 3). Peripheral spatial selectivity was assessed using the electrically evoked compound action potential (ECAP) to obtain channel-interaction functions for all activated electrodes (13 functions total). Central processing was assessed by eliciting the auditory change complex with both spatial (electrode pairs) and spectral (rippled noise) stimulus changes. Speech-perception measures included vowel discrimination and the Bamford-Kowal-Bench Speech-in-Noise test. Spatial and spectral selectivity and speech perception were expected to be poorest with MAP 1 (closest electrode spacing) and best with MAP 3 (widest electrode spacing). Relationships among the electrophysiological and speech-perception measures were evaluated using mixed-model and simple linear regression analyses.All electrophysiological measures were significantly correlated with each other and with speech scores for the mixed-model analysis, which takes into account multiple measures per person (i.e., experimental MAPs). The ECAP measures were the best predictor. In the simple linear regression analysis on MAP 3 data, only the cortical measures were significantly correlated with speech scores; spectral auditory change complex amplitude was the strongest predictor.The results suggest that both peripheral and central electrophysiological measures of spatial and spectral selectivity provide valuable information about speech perception. Clinically, it is often desirable to optimize performance for individual CI users. These results suggest that ECAP measures may be most useful for within-subject applications when multiple measures are performed to make decisions about processor options. They also suggest that if the goal is to compare performance across individuals based on a single measure, then processing central to the auditory nerve (specifically, cortical measures of discriminability) should be considered.

Project description:The structure-guided design of chloride-conducting channelrhodopsins has illuminated mechanisms underlying ion selectivity of this remarkable family of light-activated ion channels. The first generation of chloride-conducting channelrhodopsins, guided in part by development of a structure-informed electrostatic model for pore selectivity, included both the introduction of amino acids with positively charged side chains into the ion conduction pathway and the removal of residues hypothesized to support negatively charged binding sites for cations. Engineered channels indeed became chloride selective, reversing near -65 mV and enabling a new kind of optogenetic inhibition; however, these first-generation chloride-conducting channels displayed small photocurrents and were not tested for optogenetic inhibition of behavior. Here we report the validation and further development of the channelrhodopsin pore model via crystal structure-guided engineering of next-generation light-activated chloride channels (iC++) and a bistable variant (SwiChR++) with net photocurrents increased more than 15-fold under physiological conditions, reversal potential further decreased by another ∼ 15 mV, inhibition of spiking faithfully tracking chloride gradients and intrinsic cell properties, strong expression in vivo, and the initial microbial opsin channel-inhibitor-based control of freely moving behavior. We further show that inhibition by light-gated chloride channels is mediated mainly by shunting effects, which exert optogenetic control much more efficiently than the hyperpolarization induced by light-activated chloride pumps. The design and functional features of these next-generation chloride-conducting channelrhodopsins provide both chronic and acute timescale tools for reversible optogenetic inhibition, confirm fundamental predictions of the ion selectivity model, and further elucidate electrostatic and steric structure-function relationships of the light-gated pore.

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Near physiological spectral selectivity of cochlear optogenetics.

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Near physiological spectral selectivity of cochlear optogenetics.

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