text: Sept 2016 Hearing Journal
  The cochlear implant (CI) is the most successful neuroprosthesis. It has evolved from a rudimentary single channel implant in the mid-20th century to a multi-channel auditory neurostimulator that provides meaningful sound and speech perception to the majority of deaf users. A close analogue to the CI, the auditory brainstem implant (ABI) provides meaningful hearing perception to those who may not benefit from a CI due to anatomic constraints, such as neurofibromatosis 2 or cochlear nerve aplasia.
  But despite this widespread success, both the CI and ABI have significant limitations, such as variable outcomes across similar patient cohorts and deficits in understanding speech in noisy environments and in music appreciation. One likely limitation in all existing bionic devices is that electrical stimulation results in current spread and channel crosstalk; the degree of overlap among nerve fibers stimulated by adjacent CI or ABI electrodes degrades the quality of the implant's stimulus. ABI users in particular often have electrodes that cannot be used in the map due to off-target effects, resulting in facial nerve stimulation, pain, or dizziness primarily due to electrical current spread.
  Light-based stimulation is an exciting new long-term alternative to electrically-based implants that offers a theoretical advantage: light can be focused to target smaller areas while reducing the unintended consequence of current spread. Optogenetics refers to the combination of optics and genetics to control specific events within living cells, such as action potentials in neurons. It requires the modification of neurons to make them photosensitive to a specific wavelength of light and is based on the expression of light-sensitive proteins, called opsins. One specific group of opsins, called channelrhodopsins, are light-gated ion channels found in blue-green algae and control movement in response to photons of light. Opsins are delivered to specific tissues using a viral vector or other approaches, which then may be used to control cellular events (such as turning on or off a neuron -see diagram below. Upon exposure of the photosensitized neuron to a specific wavelength of light of appropriate brightness (or intensity), only cells that express the specific opsin will respond. This type of specific stimulation is in contrast to the nonspecific electric-based model.
  Several landmark studies have recently demonstrated the feasibility of optogenetic stimulation of the auditory pathways in an animal model. Notably, no deleterious effects on hearing associated with the viral injections were observed based on sound-evoked auditory brainstem responses (ABR). Taking this initial approach one step further, a research group at the Massachusetts Eye and Ear Infirmary showed that higher auditory centers were activated as a result of stimulation of opsin-expressing cochlear nucleus neurons and provided the first evidence that a brainstem implant based on light was feasible.
  Control experiments that used laser light on the auditory brainstem of animals that did not express opsins failed to show any responses along the auditory pathways.
  Behavioural studies are critical to determine whether animals that "hear the light" respond meaningfully as they do to sound-driven tasks. To this end, another team from the Massachusetts Eye and Ear showed responses based on light stimulation closely approximated an auditory midbrain implant.
  In conclusion, optogenetics has revolutionised neuroscience research in the last decade, affording unprecedented control of cellular events with millisecond precision. While existing studies largely demonstrate proof of concept of the use of optogenetics to stimulate the auditory system, many questions remain. The optogenetic promise of tissue-specificity resulting in increased number of independent channels is still largely theoretical. To address whether optogenetic-based implants may be as good or better than electrically-based implants, optical hardware needs to be substantially refined. While it is feasible to fit several traditional electrodes into an array suitable for the tiny cochlea of a mouse, this is not feasible with optrode technology based on LEDs. Indeed, to do a true comparison, light-based optrodes will need to fit within the size constraints of the auditory system. Much of this type of hardware has yet to be optimised for use in the cochlea or brainstem.
  Targeted and robust opsin delivery and expression on auditory neurons will also be pivotal in developing a successful optogenetic implant. Unlike the electrically-based CI or ABI, optical auditory implants necessitate tissue modification and gene delivery, and these approaches have yet to be demonstrated in humans. While there are ongoing clinical trials for viral gene therapy of the cochlea, this research is far from standard of care. As safe and efficient gene transfer (both viral and non-viral) of the peripheral and central auditory system develops in animal models and in human clinical trials, so too will the feasibility of an optogenetic-based auditory implant.
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