Hybrid optogenetic and electrical stimulation for greater spatial resolution and temporal fidelity of cochlear activation

Abstract

Compared to electrical stimulation, optogenetic stimulation has the potential to improve the spatial precision of neural activation in neuroprostheses, but it requires intense light and has relatively poor temporal kinetics. We tested the effect of hybrid stimulation, which is the combination of subthreshold optical and electrical stimuli, on spectral and temporal fidelity in the cochlea by recording multiunit activity in the inferior colliculus of channelrhodopsin (H134R variant) transgenic mice. Pulsed light or biphasic electrical pulses were delivered to cochlear spiral ganglion neurons of acutely deafened mice, either as individual stimuli or as hybrid stimuli for which the timing of the electrical pulse had a varied delay relative to the start of the optical pulse. Facilitation occurred when subthreshold electrical stimuli were applied at the end of, or up to 3.75 ms after subthreshold optical pulses. The spread of activation resulting from hybrid stimulation was significantly narrower than electrical-only and optical-only stimulation (p<0.01), measured at equivalent suprathreshold levels of loudness that are relevant to cochlear implant users. Furthermore, temporal fidelity, measured as maximum following rates to 300 ms pulse trains bursts up to 240 Hz, was 2.4-fold greater than optical-only stimulation (p<0.05). By significantly improving spectral resolution of electrical-and optical-only stimulation and the temporal fidelity of optical-only stimulation, hybrid stimulation has the potential to increase the number of perceptually independent stimulating channels in a cochlear implant.

Developing Fast, Red-Light Optogenetic Stimulation of Spiral Ganglion Neurons for Future Optical Cochlear Implants

“…Photosensitization of neurons can be achieved by optogenetics, i.e., expressing Channelrhodopsins (ChRs) in the plasma membrane of neurons (Nagel et al, 2003;Boyden et al, 2005). Optogenetic stimulation of the SGNs was shown to activate the auditory pathway (Hernandez et al, 2014;Duarte et al, 2018;Keppeler et al, 2018;Mager et al, 2018;Wrobel et al, 2018;Dieter et al, 2019Dieter et al, , 2020bKeppeler et al, 2020;Thompson et al, 2020) and to restore hearing in various models of deafness (Hernandez et al, 2014;Mager et al, 2018;Wrobel et al, 2018;Keppeler et al, 2020). Recent studies, characterizing the cochlear spread of excitation by recordings from the inferior colliculus, validate the advantage of optogenetic SGN stimulation over conventional electrical stimulation (Dieter et al, 2019(Dieter et al, , 2020bKeppeler et al, 2020).…”

Magnetic stimulation allows focal activation of the mouse cochlea

“…Although the STCs for bipolar electric stimulation were significantly narrower than those for monopolar stimulation in that study, both were substantially wider than STCs for acoustic stimulation (8.23- and 4.25-fold, respectively). Another study in mice ( Thompson et al, 2020 ) reported that STCs for electric stimulation were three to four times broader than those for pure tones. Thus, the wide spread of activation from electric stimulation measured here (3.14 times larger than that from monotones) is in good agreement with previous reports.…”

Cochlear implant research and development in the 21st century: A critical update

“…The temporal encoding of pulse rate with optical stimulation is not as good as with electrical or acoustic stimulation and depends strongly on the choice of opsin (Dieter et al, 2020). One interesting approach is to combine electrical and optical stimulation, leading to (in the mouse inferior colliculus) improved spatial and temporal coding compared to optical stimulation alone (Thompson et al, 2020)).…”