Project

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Gapless man:machine interface in the inner ear

English title Gapless man:machine interface in the inner ear
Applicant Senn Pascal
Number 170193
Funding scheme Project funding
Research institution Département de Neurosciences Cliniques Hôpitaux Universitaires de Genève Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.10.2017 - 31.03.2021
Approved amount 474'000.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Otorhinolaryngology

Keywords (7)

neuroprosthesis; hearing loss; hearing; auditory nerve; deafness; cochlear implant; regenerative neuroscience

Lay Summary (German)

Lead
Hörprothesen, sogenannte Cochlea-Implantate, erlauben ertaubten Menschen wieder zu hören, haben aber noch wichtige Limitationen insbesondere bei der akustischen Auflösung und beim Stromverbrauch. Unser Projekt zielt darauf ab, durch die Verbesserung der Schnittstelle zwischen der Cochlea-Implantat-Elektrode und den Hörnervenzellen im Innenohr eine bessere Stimulation des Hörnerven und dadurch ein besseres Hören bei geringerem Stromverbrauch zu erreichen.
Lay summary

Mehr als 5% der Weltbevölkerung, also um die 360 Millionen Menschen, leiden an invalidisierendem Hörverlust. Linderung bringen Hörgeräte und in schweren Fällen Hörprothesen, sogenannte Cochlea-Implantate (CI). Trotz der Erfolge verbleiben einige wichtige Einschränkungen, insbesondere bei der akustischen Auflösung und dem hohen Energieverbrauch der CI-Systeme. Ein Hauptgrund für diese Limitationen liegt beim anatomischen Abstand zwischen der CI-Elektrode, die chirurgisch ins Innenohr implantiert wird, und den Hörnervenfasern, welche durch das Implantat stimuliert werden.

Das Hauptziel dieses Projektes ist die Schaffung einer abstandslosen, robusten Schnittstelle zwischen der CI-Elektrode und den Hörnervenzellen im Innenohr. Dazu ist es notwendig Nervenwachstumsfaktoren, Steuerungselemente und geeignete Elektrodenoberflächen chirurgisch ins Innenohr einzubringen und das Zusammenspiel dieser Faktoren vollständig zu kontrollieren. Parallel dazu werden optimale Stimulationsparameter für menschliche Hörnervenzellen in vitro erarbeitet. Schlussendlich wird ein Langzeitstimulationsversuch über die abstandslose Schnittstelle im Tiermodell durchgeführt mit dem Ziel, die physiologischen Einflüsse auf das Hörvermögen und die biologischen Konsequenzen zu verstehen.

Gelingt die Schaffung der abstandslosen Schnittstelle, ergeben sich neue Möglichkeiten für eine bessere Nervenstimulation mit einer höheren Anzahl Stimulationskanäle (beim visuellen System würde dies einer erhöhten Anzahl Pixel entsprechen) und geringerem Stromverbrauch, welcher kleineren und kosteneffizienteren Bauformen der CI-Systeme Vorschub leisten könnte

Das Fernziel dieses Projektes ist eine Verbesserung des Cochlea-Implantats, um ertaubten Menschen ein besseres Hören, mit kleineren, ästhetisch ansprechenderen und energie-effizienteren Implantaten zu ermöglichen.


Direct link to Lay Summary Last update: 23.08.2017

Responsible applicant and co-applicants

Employees

Publications

Publication
Intrinsically Self-renewing Neuroprogenitors From the A/J Mouse Spiral Ganglion as Virtually Unlimited Source of Mature Auditory Neurons
Rousset Francis, B. C. Kokje Vivianne, Sipione Rebecca, Schmidbauer Dominik, Nacher-Soler German, Ilmjärv Sten, Coelho Marta, Fink Stefan, Voruz François, El Chemaly Antoun, Marteyn Antoine, Löwenheim Hubert, Krause Karl-Heinz, Müller Marcus, Glückert Rudolf, Senn Pascal (2020), Intrinsically Self-renewing Neuroprogenitors From the A/J Mouse Spiral Ganglion as Virtually Unlimited Source of Mature Auditory Neurons, in Frontiers in Cellular Neuroscience, 14, 1-15.
Age-Dependency of Neurite Outgrowth in Postnatal Mouse Cochlear Spiral Ganglion Explants
Frick Claudia, Fink Stefan, Schmidbauer Dominik, Rousset Francis, Eickhoff Holger, Tropitzsch Anke, Kramer Benedikt, Senn Pascal, Glueckert Rudolf, Rask-Andersen Helge, Wiesmüller Karl-Heinz, Löwenheim Hubert, Müller Marcus (2020), Age-Dependency of Neurite Outgrowth in Postnatal Mouse Cochlear Spiral Ganglion Explants, in Brain Sciences, 10(9), 580-580.

Datasets

E-MTAB-9441 - RNAseq of A/J mice spiral ganglion derived neurospheres vs differentiated auditory neurons

Author Rousset, Francis
Publication date 29.08.2020
Persistent Identifier (PID) E-MTAB-9441
Repository ArrayExpress
Abstract
Sphere-forming progenitor cells can be isolated from the fetal and adult mammalian inner ear and give rise to inner ear specific cell types in vitro. Here, we provide phenotypical and functional characterization of a new pool of auditory progenitors as sustainable source for sphere-derived auditory neurons. The so-called phoenix auditory neuroprogenitors, isolated from the A/J mouse spiral ganglion, exhibit nearly unlimited intrinsic self-renewal properties (beyond 40 passages). At any passage, phoenix spheres can be efficiently differentiated by withdrawing growth factors into mature spiral ganglion cells, expressing both neurons and glial cells phenotypic markers and exhibiting similar functional properties as mouse spiral ganglion explants and human sphere-derived spiral ganglion cells. The present dataset includes RNAseq-based transcriptome analysis of phoenix auditory neurons following 7 days of differentiation. mRNA levels in differentiated cells are expressed relatively to neuroprogenitor spheres of equivalent passage (paired samples at passage 12, 21 and 36)

Collaboration

Group / person Country
Types of collaboration
Tübingen Hearing Research Centre Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Universitätsklinik für HNO, Medizinische Univ. Innsbruck Austria (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
ARO meeting Poster Exogenous BDNF and NT-3 in mouse explant cultures: Only a neural survival factor or also promoting axonal outgrowth 01.02.2020 San Jose, United States of America Glückert Rudolf;
ISIET Talk given at a conference Defined BDNF and NT-3 Growth Factor Cocktail Enhanced Neurite Outgrowth in a Postnatal Day 7 (adult-like) Murine In Vitro Spiral Ganglion Explant Model 06.11.2019 Hannover, Germany Löwenheim Hubert;
Inner ear biology meeting Poster Exogenous BDNF and NT-3 in mouse explant cultures: Only a neural survival factor or also promoting axonal outgrowth? 08.09.2019 Padova, Italy Glückert Rudolf;
Inner ear biology meeting Poster Defined BDNF and NT-3 Growth Factor Cocktail Enhanced Neurite Outgrowth in a Postnatal Day 7 (adult-like) Murine In Vitro Spiral Ganglion Explant Model 08.09.2019 Padova, Italy Löwenheim Hubert;
ARO meeting Poster Combined BDNF and NT-3 Neurotrophin Cocktail Stimulates Neurite Outgrowth in an In Vitro Mouse Spiral Ganglion Explant Model 11.02.2019 Baltimore, United States of America Löwenheim Hubert;


Abstract

Over 5% of the world’s population - 360 Million people - suffer from disabling hearing loss. In severe forms, the auditory function can be restored by a neuroprosthesis called cochlear implant (CI), which functionally replaces lost inner ear sensory cells by directly stimulating the auditory nerve fibers. Despite the success of these devices, some limitations remain, including suboptimal auditory resolution and high energy consumption, which are mainly due to the anatomical gap between the implanted electrode array in the cochlea and the auditory neurons nearby. Within a recently completed, multinational EU-FP7 project coordinated by the main applicant PD Dr. Senn (www.nanoci.org), proof of principle for overcoming the anatomical gap by guided growth of auditory nerve fibers towards the electrode arrays has been obtained in vivo. In addition, in vitro experiments have shown a reduction of the stimulus energy by a factor of 5, if the distance of the auditory neurons from the electrode was eliminated. Within the proposed project, we intend to improve the gapless interface through optimized growth factor guidance in combination with chronic electrical stimulation and detailed morphological, biochemical and electrophysiological characterization of regrown auditory neurons in vitro and in vivo. Native and stem cell generated, donated human auditory neurons will be used in vitro for validation. The ultimate goal of the proposed project is to assess the potential of the gapless interface between auditory neurons and the cochlear implant electrodes through chronic electrical stimulation in vivo. If successful, the proposed project may lead to more energy-efficient cochlear implant systems with higher auditory resolution and improved sound quality. Due to the complexity and the ambitious goals of the proposed project, a tri-national, multi-centric approach has been chosen with the lead-agency at the University of Geneva and the collaboration partners at the Universities of Tübingen and Innsbruck (DACH-project). Together we form a competitive team with synergistic and complementary experience in auditory neuroscience able to solve the challenging tasks.
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