Optogenetic Stimulation of the Auditory Nerve

Abstract

Direct electrical stimulation of spiral ganglion neurons (SGNs) by cochlear implants (CIs) enables open speech comprehension in the majority of implanted deaf subjects(1-) (6). Nonetheless, sound coding with current CIs has poor frequency and intensity resolution due to broad current spread from each electrode contact activating a large number of SGNs along the tonotopic axis of the cochlea(7-) (9). Optical stimulation is proposed as an alternative to electrical stimulation that promises spatially more confined activation of SGNs and, hence, higher frequency resolution of coding. In recent years, direct infrared illumination of the cochlea has been used to evoke responses in the auditory nerve(10). Nevertheless it requires higher energies than electrical stimulation(10,11) and uncertainty remains as to the underlying mechanism(12). Here we describe a method based on optogenetics to stimulate SGNs with low intensity blue light, using transgenic mice with neuronal expression of channelrhodopsin 2 (ChR2)(13) or virus-mediated expression of the ChR2-variant CatCh(14). We used micro-light emitting diodes (µLEDs) and fiber-coupled lasers to stimulate ChR2-expressing SGNs through a small artificial opening (cochleostomy) or the round window. We assayed the responses by scalp recordings of light-evoked potentials (optogenetic auditory brainstem response: oABR) or by microelectrode recordings from the auditory pathway and compared them with acoustic and electrical stimulation.

Optogenetic stimulation of the cochlea—A review of mechanisms, measurements, and first models

“…In the case of CIs, the spread of spatial excitation limits the number of effective (independent) stimulation channels. Experimentally, optogenetic stimulation of the auditory nerve so far was only achieved by Hernandez et al (2014a). In these experiments, the spatial spread of stimulation was only indirectly accessible with recordings in the inferior colliculus.…”

“…A solid knowledge of the light reaching SGNs is crucial to understand where and how selectively these neurons are excited, especially if we consider that they have an extended structure and run from the osseous spiral lamina to the center of the modiolus and then from apex to base inside the modiolus. When we transfer the results of Hernandez et al (2014a) to the conditions in the human cochlea, the extent of spatial excitation is expected to be about 250 μm only if the LEDs can be placed directly on the modiolar bone (215 μm distance from the LED to the nerve). If it would be possible to insert a dense LED array up to 25 mm into the human cochlea, we could realize about 100 independent stimulation channels which is one order of magnitude more than what can be achieved with electrical stimulation (Friesen et al 2001).…”

“…Research groups now make this technology available for neuroprosthetic applications which suggests itself for retinal implants (Lagali et al 2008;Ivanova et al 2010). For cochlear implants (CIs), optical stimulation promises major advantages, in particular a substantial increase in the number of independent stimulation channels (Hernandez et al 2014a;Jeschke and Moser 2015). This is very attractive for CIs, as present electrical stimulation with an intracochlear CONTACT Robin S. Weiss robin.weiss@tum.de Technical University of Munich, Electrical and Computer Engineering, Boltzmannstr.…”

“…This is illustrated in Figure 1. Therefore, optical stimulation has the potential to target well-defined SGN populations which would allow a much higher number of independent stimulation channels (Hernandez et al 2014a). The expectation is that this jump in frequency resolution improves the sound quality of CIs enormously.…”

“…As the depolarizing currents are high enough to selectively excite neurons which have been genetically programmed to express this opsin, ChR2 has become a widely used tool in neuroscience. The discovery of channelrhodopsins led to a new field in neuroscience that allows scientists to research specific brain functions in in-vitro cultures but also in behavioral studies in animals (Tye and Deisseroth 2012;Nagel et al 2005;Liewald et al 2008;Zhang et al 2006;Cardin et al 2010;Hernandez et al 2014a).…”