In the control room for hearing with light

(mbexc/umg) Optogenetics, the control of genetically modified cells with light, has revolutionized the life sciences and medicine. It allows the activity of cells and their networks to be controlled in a targeted manner via light pulses. This opens up completely new perspectives for the therapy of dysfunctions of sensory systems, such as hearing and vision. The potential of optogenetic treatments for the functional recovery of sensory systems and their clinical feasibility have recently been demonstrated for the visual system. The optogenetic treatment of hearing loss and deafness by the optical cochlear implant (oCI) is still in the preclinical stage. Preclinical studies and simulations suggest that hearing with light has the potential to enable near-physiological auditory impression, including the recognition of emotional tones and complex melodies.

Dr. Antoine Tarquin Huet, Junior Fellow at the Göttingen Cluster of Excellence Multiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells (MBExC), explores the requirements that must be met for the clinical use of the oCI in humans. “Hearing with light requires the oCI to convert acoustic signals into a pattern of light signals, which then stimulate the neurons in the cochlea in an appropriate manner. Optogenetic stimulation must be precisely tailored to the coding properties of the auditory nerve cells", says Huet from the Institute for Auditory Neuroscience of the University Medical Center Göttingen (UMG). "In the current study, we defined appropriate stimulation parameters within which the control of auditory neurons using future optogenetic prostheses, such as the oCI, light is plausible.“ In their recently published study, the Göttingen hearing researchers moreover describe how a fast and reliable characterization of future optogenetic tools can be achieved, which can then be used to study the processing of neuronal signals between the ear and the brain. The findings were recently published in the scientific journal “Brain Stimulation”.

Original publication: Mittring A, Moser T, Huet AT (2023) Graded optogenetic activation of the auditory pathway for hearing restoration. Brain Stimulation (2023) S1935-861X(23)01673-X. https://doi.org/10.1016/j.brs.2023.01.1671.

Background information: Hearing with light and the advantages

The restoration of hearing via an optogenetic apporach allows to bypass dysfunctional or missing sensory cells by targeting the activity of downstream auditory neurons with light pulses. The approach requires a gene therapy in which the auditory nerve cells are made light-sensitive by inserting light-sensitive ion channels, so-called channelrhodopsins. The implantable optical stimulator of the oCI is used for targeted stimulation with light. This leads to the opening of the channels and an influx of ions, an action potential occurs, and the nerve cell is electrically excited. Light pulses for stimulating the auditory nerve can be used much more precisely than electricity, thus enabling to activate much smaller areas with fewer auditory nerve cells than with the electrical CI used so far. The cellular specificity and spatial confinement of optogenetic stimulation promise to improve functional recovery far beyond what is possible with current electrical cochlear implants.

Research findings in detail

The prerequisite for restoring hearing with light is that the optical cochlear implant translates the incoming sound information into light signals, which in turn activate the nerve cells in the cochlea in a suitable manner. To pave the way for clinical trials and thus future use in humans, the first step is to define the boundaries within which the control of nerve cell activity in the cochlea can succeed. "Optimal control of neuronal activity with light is far from trivial," Huet said. "It requires good tuning of the production of the channelrhodopsins used and their cellular membrane incorporation, optimal matching of optogenetic stimulation parameters to the coding properties of the targeted neuron population, and the right choice of laser diodes."

In their study, the Göttingen scientists present a parameter range for the optogenetic control of neurons and applied it to the auditory pathway, which requires high temporal accuracy of stimulation. They studied how light pulses of defined intensity and duration control the activation of individual auditory neurons in the cochlea of mice. To that end, they introduced Chronos, a naturally occurring channelrhodopsin that is able to respond extremely quickly to light stimulation, into the spiral ganglion neurons (SGN) of the mouse cochlea. They demonstrated that by adjusting the duration of light pulses a graded activation of auditory neurons can be achieved. This is of interest for the optimal use of the laser diodes. Moreover, they defined the optimal duration as well as an upper limit for the frequency of light pulses under the given conditions.

Interestingly, the population of optogenetically controlled auditory neurons exhibited great diversity. "From a theoretical point of view, this functional diversity is a key factor that expands the amount of encoded information and increases its reliability," Huet says. In addition, the findings indicate that neurons downstream of the SGNs could be excited in a near-physiological manner when SGNs are optogenetically stimulated. The findings of the Göttingen hearing researchers will pave the way for designing the sound-coding strategies of future optical cochlear implants.

Dr. Antoine Tarquin Huet is supported as an outstanding postdoctoral researcher  by the Cluster of Exellence Mutliscale Bioimaging to accelerate his way towards scientific independence. Huet was selected through an international call for applications for the position of Junior Fellow to contribute with his research to the goals of the MBExC. With the „Auditory Circuit Lab“ he is setting up an independent research group at the Institute for Auditory Neurosciences headed by MBExC speaker Prof. Dr. Tobias Moser, pioneer in hearing restoration research with the optical cochlear implant. Moreover, Huet is a member of the Hertha Sponer College, which was established at the MBExC to educate a new generation of integrative researchers who combine basic research with biomedicine.

The Göttingen Cluster of Excellence Multiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells (MBExC) is funded since January 2019 in the framework of the Excellence Strategy of the German Federal and State Governments. Applying a unique and multiscale approach, MBExC investigates the disease-relevant functional units of electrically active cells of heart and brain, from the molecular to the organ level. The MBExC unites numerous partners from the university and extra-university institutions in Göttingen. The overall goal: to understand the relationship between heart and brain diseases, to link basic and clinical research, and thus to develop new therapeutic and diagnostic approaches with social implications.

FURTHER INFORMATION
about the MBExC: https://mbexc.de/
about the Auditory Circuit Lab at the Institute for Auditory Neuroscience: http://www.auditory-neuroscience.uni-goettingen.de/group_Huet.html
about the Hertha Sponer College: https://mbexc.de/careers/hertha-sponer-college/

CONTACT
University Medical Center Göttingen, University of Göttingen
Dr. Antoine Tarquin Huet
Auditory Circuit Lab
Institute for Auditory Neuroscience
Robert-Koch-Straße 40, 37075 Göttingen
Phone +49 551 / 39-22604; E-mail: antoine.huet@med.uni-goettingen.de

Cluster of Excellence Multiscale Bioimaging (MBExC)
Dr. Heike Conrad (Science communication)
Phone: +49 551 / 39-61305; E-mail: heike.conrad(at)med.uni-goettingen.de