Thin-film micro-electrode stimulation of the cochlea in rats exposed to aminoglycoside induced hearing loss

Allitt, Benjamin J.; Harris, Alexander R.; Morgan, Simeon J.; Clark, Graeme M.; Paolini, Antonio G.

doi:10.1016/j.heares.2015.10.003

Cited by 11 publications

(9 citation statements)

References 39 publications

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“…The output DR of individual multi-units in response to sound (21.4 dB) and electrical stimulation (6.9 and 8.3 dB for monopolar and bipolar stimulations) are in good agreement with literature values: an average DR of 20 dB per single unit in response to sound has been reported for the gerbil IC and DRs between 6.7 and 7.6 dB have been reported upon stimulation with different kinds of eCIs in the rat IC 31–33 . DR comparison of optogenetic to electrical stimulation is confounded by the fact that we did not find saturation for most multi-units at the light intensities amenable to our setup (Fig.…”

Section: Discussionsupporting

confidence: 90%

Near physiological spectral selectivity of cochlear optogenetics

et al. 2019

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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.

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Section: Discussionsupporting

confidence: 90%

Near physiological spectral selectivity of cochlear optogenetics

et al. 2019

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“…6 These observations may be in part explained by longitudinal spread of electric current from individual electrodes, resulting in channel interaction and reduced spectral resolution. 7,8 Optogenetics enables the precise modulation of cellular activity with optical stimulation following genetic manipulation of neurons to express microbial transmembrane proteins called opsins. Several studies have explored optogenetics as an alternative stimulus paradigm for auditory implants.…”

Section: Introductionmentioning

confidence: 99%

Ancestral Adeno-Associated Virus Vector Delivery of Opsins to Spiral Ganglion Neurons: Implications for Optogenetic Cochlear Implants

et al. 2018

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Optogenetics is a transformative technology based on light-sensitive microbial proteins, known as opsins, that enable precise modulation of neuronal activity with pulsed radiant energy. Optogenetics has been proposed as a means to improve auditory implant outcomes by reducing channel interaction and increasing electrode density, but the introduction of opsins into cochlear spiral ganglion neurons (SGNs) in vivo has been challenging. Here we test opsin delivery using a synthetically developed ancestral adeno-associated virus (AAV) vector called Anc80L65. Wild-type C57BL/6 mouse pups were injected via the round window of cochlea with Anc80L65 carrying opsin Chronos under the control of a CAG promoter. Following an incubation of 6-22 weeks, pulsed blue light was delivered to cochlear SGNs via a cochleosotomy approach and flexible optical fiber. Optically evoked auditory brainstem responses (oABRs) and multiunit activity in inferior colliculus (IC) were observed. Post-experiment cochlear histology demonstrated opsin expression in SGNs (mean = 74%), with an even distribution of opsin along the cochlear basal/apical gradient. This study is the first to describe robust SGN transduction, opsin expression, and optically evoked auditory electrophysiology in neonatal mice. Ultimately, this work may provide the basis for a new generation of cochlear implant based on light.

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“…Thin film electrode technology allows for miniaturization and increasing the density of electrode sites (Allitt et al, 2016; Rodger et al, 2008). The thin-film array tested here, using the technology described previously (Guex et al, 2015), accommodates 20 microelectrodes within 2 mm 2 , an electrode density much higher than that of clinical ABIs.…”

Section: Discussionmentioning

confidence: 99%

Auditory brainstem stimulation with a conformable microfabricated array elicits responses with tonotopically organized components

et al. 2019

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Auditory brainstem implants (ABIs) restore hearing to deaf individuals not eligible for cochlear implants. Speech comprehension in ABI users is generally poor compared to that of cochlear implant users, and side effects are common. The poor performance may result from activating broad areas and multiple neuronal populations of the cochlear nucleus, however detailed studies of the responses to surface stimulation of the cochlear nucleus are lacking. A conformable electrode array was microfabricated to fit on the rat’s dorsal cochlear nucleus (DCN). It hosts 20 small electrodes (each 100 μm diam.). The array was tested by recording evoked potentials and neural activity along the tonotopic axis of the inferior colliculus (IC). Almost all bipolar electrode pairs elicited responses, in some cases with an even, or relatively constant, pattern of thresholds and supra-threshold measures along the long axis of the array. This pattern suggests that conformable arrays can provide relatively constant excitation along the surface of the DCN and thus might decrease the ABI side effects caused by spread of high current to adjacent structures. We also examined tonotopic patterns of the IC responses. Compared to sound-evoked responses, electrically-evoked response mappings had less tonotopic organization and were broader in width. They became more tonotopic when the evoked activity common to all electrodes and the late phase of response were subtracted out, perhaps because the remaining activity is from tonotopically organized principal cells of the DCN. Responses became less tonotopic when inter-electrode distance was increased from 400 µm to 800 µm but were relatively unaffected by changing to monopolar stimulation. The results illustrate the challenges of using a surface array to present tonotopic cues and improve speech comprehension in humans who use the ABI.

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Thin-film micro-electrode stimulation of the cochlea in rats exposed to aminoglycoside induced hearing loss

Cited by 11 publications

References 39 publications

Near physiological spectral selectivity of cochlear optogenetics

Near physiological spectral selectivity of cochlear optogenetics

Ancestral Adeno-Associated Virus Vector Delivery of Opsins to Spiral Ganglion Neurons: Implications for Optogenetic Cochlear Implants

Auditory brainstem stimulation with a conformable microfabricated array elicits responses with tonotopically organized components

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