Hearing loss affects millions of people worldwide. In cases of pronounced cochlear dysfunction, an electrical cochlear implant (eCI) can partially restore hearing sensation by electrically stimulating the auditory nerve. Until now, the eCI is the most successful and broadly used neuroprosthesis, with more than 1 million users worldwide (WHO, 2021). However, eCI hearing is far from normal: eCI users can typically not comprehend speech in noisy environments, because the electrical signal spreads widely and excites a large number of neurons of the auditory nerve, which limits the number of separate perceptual channels. Using optogenetics, it is possible to stimulate the auditory nerve using an optical cochlear implant (oCI). As light spread can be better confined in space, oCIs offer lower spread of excitation and, hence, greater frequency selectivity. This way, future clinical oCIs promise more perceptual channels, allowing for more pitch appreciation and better understanding of speech in noise. However, there are many challenges in the development of the oCI en route to clinical application. Importantly, we are currently missing a holistic assessment tool for preclinical efficacy which could serve oCI optimization. I will develop a set of methodological and computational tools to assess the oCI performance in vivo, in the Mongolian gerbil. First, I will use the brainstem responses to map the frequency activation of separate optical channels. Second, I will develop predictive models that derive the optogenetically and acoustically evoked responses of the midbrain, applying machine learning techniques. Third, I will use the above-mentioned tools to identify the optimal coding strategy for the oCI. This project will accelerate the development of the oCI, and provide benchmarking standards for the clinical trials of optical neural implants.

Understanding how neural circuits process and encode information is a fundamental goal in neuroscience. For the neural network of the retina, such knowledge is also of concrete importance for the development of vision restoration therapies for patients suffering from degeneration of photoreceptors. Artificial stimulation of retinal neurons through electronic implants or inserted light-sensitive proteins (“optogenetics”) aims at reconstructing natural transmission of visual information to the brain. Recreating natural retinal activity, however, will require a thorough understanding of the complex and diverse neural code of the retina. The challenge lies in deciphering the various nonlinear operations and dynamics in the around 30 parallel signalling streams that emerge from the retina, represented by as many types of ganglion cells, the retina’s output neurons. The CODE4Vision project will tackle this challenge by identifying the effective connectivity between the different types of retinal ganglion cells and their excitatory presynaptic partners, bipolar cells, and by determining the features of information processing between these neuronal layers. We will characterize the layout of bipolar cell inputs to large populations of ganglion cells with novel analyses that we derive from computational statistics and machine learning. We will then study the nonlinear and dynamical features of these connections by designing closed-loop experiments that automatically adjust visual stimuli to the identified layout of bipolar cells. These analyses will be supplemented by direct measurements of connections through simultaneous bipolar and ganglion cell recordings. The results will pave the way towards new models of how the retina encodes natural visual stimuli. Finally, we will apply this knowledge to mouse models of optogenetic vision restoration in order to develop stimulation schemes that emulate natural retinal stimulus encoding.

The optical cochlear implant (oCI) aims to restore near natural hearing in profoundly hearing impaired and deaf patients. Sound perception will be restored through an implantable medical device in combination with a gene therapy medicinal product. Thereby the auditory nerve is stimulated directly through focused light replacing the dysfunctional or absent hair cells. This is achieved through combination of micro-scale light emitter technology and precise neural control through expression of light-gated ion channels in the auditory nerve (called optogenetics). Here, we propose to prove feasibility of an optical waveguide modules for future optical cochlear implants. Building on fabricating micro-scaled waveguide arrays, multi-beam laser diode emitters, we plan to couple them via micro-lens arrays in a compact multi-channel optical module for testing the feasibility of miniaturization and integration of the optical components. Preclinical validation shall be performed in rodents. The proposed waveguide-based optical module combines several aspects, which makes it a candidate for later clinical application. The optical emitters can be safely integrated in the hermetically sealed titanium package housing the internal oCI electronics. Thus, there is no need to directly insert the emitters in the cochlear turns, which mitigates the risk of heat impact on the patient during optical stimulation. Furthermore, emerging red light activated opsins can be addressed by readily available red laser diode technology.