Duque Afonso, Carlos Javier

English

Five per cent of the world population suffers nowadays from some kind of disabling hearing impairment, and 90% out of them is due to a defective functioning of the first step in the transduction of the soundwave into a neural code: the organ of Corti and the spiral ganglion neurons. The development of the most successful neuroprosthetic device, the cochlear implant, has allowed patients to accomplish fair speech comprehension, but has failed in providing speech comprehension in noisy environments, good frequency discrimination and music and prosody appreciation. The most prominent limitation of the current electrical cochlear implant is the lateral spread of the electrical stimulus in the ionic medium of the inner ear, that reduces the number of independent stimulation channels. One promising, yet experimental, alternative is the use of light and optogenetics. Since light can be better focused than the electrical pulses, the potential crosstalk between channels is smaller and the number of independent ones is potentially bigger. However, in order to be able to stimulate the auditory neurons with light, they have to express a light sensitive ionic channel, known as opsins, delivered by viral vectors injected in the inner ear. Furthermore, an optimal optogenetic stimulation of the cochlea would need very fast and sensitive channels, that allow the submilisecond precision needed to convey auditory information to the central nervous system. In the lab we have shown the feasibility of using this modality of stimulation to activate the auditory pathway. However, some questions remain to be answered, like how is the 3D illumination profile of the light sources that we use or could use in the future or how is the precise distribution of the expression levels along the cochlea. Thus, in this thesis, I will present the effort to develop and apply a series of tools to characterize the optogenetic stimulation of the cochlea. We have developed a Monte-Carlo simulation to estimate the irradiance profile of various sources (including the optical fibers used in vivo experiments, a proof of concept of an optimal one or the μLEDs that the first optical cochlear implant might carry). In addition, I have optimized a tissue clearing protocol, cDISCO, and developed a computational workflow to study the 3D distribution of GFP (as a proxy of the transduction efficiency) as a function of the tonotopic position. We expect that these tools help us to understand better our stimulation paradigm and to plan future proof of concepts.2020-08-2

Georg-August-University Göttingen

Development and Application of Tools for the Characterization of the Optogenetics Stimulation of the Cochlea

https://ediss.uni-goettingen.de/bitstream/21.11130/00-1735-0000-0005-1424-C/1/FinalThesis_library_CD_distribucionElectronica_nocv.pdf

Development and Application of Tools for the Characterization of the Optogenetics Stimulation of the Cochlea

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Georg-August-University Göttingen