Dans la cochlée, la réponse couplée de sa structure et de son fluide interne peut être représentée sous la forme d’une onde dont les caractéristiques varient en fonction de la position longitudinale. La méthode asymptotique Wentzel-Kramers-Brillouin est adaptée à la modélisation de ce type d’onde. Dans un premier temps, cette méthode est reprise. Un modèle numérique est également développé et les résultats des deux méthodes sont comparés. Dans un deuxième temps, la métohde Wentzel-Kramers-Brillouin est améliorée afin de prendre en compte le couplage entre plusieurs ondes. Le couplage d’un mode propagatif avec des modes évanescents est réalisé et validé. Dans la cochlée, la stimulation des cellules cillées résulte d’un mouvement de cisaillement de la membrane tectoriale et de flexion de la membrane basilaire. Le couplage entre ces deux modes de déformation est encore peu connu et offre une perspective intéressante. Dans un troisième temps, une nouvelle méthode couplant la méthode Wentzel-Kramesr Brillouin et une méthode numérique est développée et validée afin de déterminer des modes transverses de propagation. Cette méthode est appliquée à la mécanique cochléaire et un mode de flexion de la membrane basilaire et un mode relatif à un mouvement de cisaillement de la membrane tectoriale sont déterminés. Enfin, une expérience inspirée des cochlées artificielles est conçue et réalisée. La propagation d’ondes est observée et la tonotopie est mesurée et comparée aux modèles. Afin de limiter la réflexion des ondes et de faciliter la mesure, une combinaison originale du trou noir acoustique avec une lame de largeur variable est utilisée. / The cochlea is the organ of hearing for humans and mammals. It is often modelled as an inhomogeneous waveguide. A travelling wave propagates along the fluid structure coupled waveguide. The mechanical impedance of the structure is varying and provides a frequency place relation. The asymptotic method Wentzel-Kramers-Brillouin allows to solve for the basilar membrane vibration. The evanescents modes are taken into account to provide a better representation compared to the numerical models. As a second step, the finite elements method is used to solve for the transversal modes while the WKB Approximation deals with the longitudinal propagation. The first flexural mode of the basilar membrane is shown. The second propagative mode reveals a shearing motion of the tectorial membrane which can help stimulating the hair cells. An over-size artificial cochlea is designed and built. Thanks to an acoustic black hole, used as a anechoic end, travelling waves are observed on this device. Reflected waves are attenuated and the interferences with incident waves reduced. Mode coupling could be applied not only to evanescent modes but also to propagatives ones. Perspectives for the adaptation of the WKB method to fluid structure inhomogeneous waveguides, and particularly to the immersed acoustic black hole, seem to be very promising.

Das Innenohr des Säugetieres ist ein hochspezialisiertes sensorisches System, das durch ein komplexes mechanisches Verhalten gekennzeichnet ist. Neben der komplizierten Morphometrie und Geometrie kommen auch dem richtungsabhängigen Materialverhalten eine wesentliche Bedeutung zu. Es zeigt sich, daß im Cortischen Organ mit der äußeren Haarsinneszelle ein Zelltyp vorliegt, der durch seine physikalischen Eigenschaften das Gesamtverhalten des Innenohres maßgeblich beeinflußt. Wie jede tierische Zelle weist die äußere Haarsinneszelle als biomechanisches System eine heterogene Mikrostruktur auf. Vom mechanischen Standpunkt aus gesehen, ist neben der mehrschichtigen basolateralen Zellwand jede Einzelzelle durch ein viskoses inneres Fluid (Zellplasma) und einen Zellkern (Nukleus) gekennzeichnet. Die resultierenden mechanischen Eigenschaften des Gesamtsystems ”äußere Haarsinneszelle” können durch Experimente und eine geeignete Modellierung determiniert werden. In dieser Arbeit wird ein neuer Ansatz zur Bestimmung der viskoelastischen Materialeigenschaften der basolateralen Wand vorgestellt. Durch Anwendung einer effektiven Fluid-Struktur-Interaktion wird das Gesamtsystem geschlossen untersucht und eine umfangreiche Materialparameterstudie durchgeführt. Dabei werden im Rahmen der Kontinuumsmechanik gültige Materialgesetze angewendet. Das durch partielle Differentialgleichungen formulierte mechanische Feldproblem wird im Rahmen der Finiten-Elemente-Methode approximiert, was zu einem linearen Gleichungssystem führt. Auf dieser Grundlage wird ein Finite-Elemente-Modell der äußeren Haarsinneszelle entwickelt. Die zur Beschreibung notwendigen Systemmatrizen – insbesondere die Dämpfungsmatrix – basieren dabei vollständig auf einem viskoelastischen Materialgesetz. Die benutzte Methodik läßt weiterhin eine effiziente Berechnung im Frequenzbereich zu. Es zeigt sich, daß eine spezielle Dämpfungsformulierung die experimentell bestimmten dynamischen Eigenschaften der Zelle adäquat widerspiegelt. Eine Analyse auf Materialgesetzebene zeigt, daß dafür reine Schubdämpfung und damit eine spezielle Anisotropie im Viskositätstensor verantwortlich ist. Diese Eigenschaft bestimmt das dynamische Verhalten der äußeren Haarsinneszelle bis mindestens 10 kHz und liegt damit im Hörbereich. Der Modellierung der Zelle geht eine angepaßte Auswertung der experimentell ermittelten Daten voraus. Die mechanisch geeignete Auswertung der zugrundeliegenden Experimente weist dabei auf mögliche Fehlerquellen bei der Analyse der Rohdaten hin. Das hat zur Konsequenz, daß der experimentellen Umgebung die gleiche Aufmerksamkeit geschenkt werden muß wie dem Meßobjekt selbst. Nur so kann eine geeignete Extraktion der für das Meßobjekt spezifischen Eigenschaften erfolgen.

Master of Science / Department of Anatomy and Physiology / Daniel C. Marcus / Sensory transduction in the cochlea depends on regulated ion secretion and absorption. Results of whole-organ experiments suggested that Reissner’s membrane may play a role in the control of luminal Cl-. We tested for the presence of Cl- transport pathways in isolated mouse Reissner’s membrane using whole-cell patch clamp recordings and gene transcript analyses using RT-PCR. The current-voltage (I-V) relationship in the presence of symmetrical NMDG-Cl was strongly inward-rectifying at negative voltages, with a small outward current at positive voltages. The inward-rectifying component of the I-V curve had several properties similar to those of the ClC-2 Cl- channel. It was stimulated by extracellular acidity and inhibited by extracellular Cd2+, Zn2+, and intracellular ClC-2 antibody. Channel transcripts expressed in Reissner’s membrane include ClC-2, Slc26a7 and ClC-Ka, but not Cftr, ClC-1, ClCa1, ClCa2, ClCa3, ClCa4, Slc26a9, ClC-Kb, Best1, Best2, Best3 or the beta-subunit of ClC-K, barttin. ClC-2 is the only molecularly-identified channel present that is a strong inward rectifier. This thesis incorporates the publication by K.X. Kim and D.C. Marcus, Inward-rectifier chloride currents in Reissner’s membrane epithelial cells. Biochem. Biophys. Res. Commun. 394 (2010) 434-438, with permission of the publisher Elsevier, and is the first report of conductive Cl- transport in epithelial cells of Reissner’s membrane and is consistent with an important role in endolymph anion homeostasis.

Bei der Anpassung eines Cochlea-Implantates (CI) entscheidet der Patient über die Lautstärke, mit der das CI ihm seine akustische Umwelt präsentiert. Mit der Methode der „kategorialen Lautheitsskalierung“ wurden Lautheitsurteile unilateraler CI-Träger ermittelt und ausgewertet. 26 unilateral versorgte CI-Träger beurteilten in 4 Versuchsabschnitten je einen Stimulustyp, der 169 mal mit 13 unterschiedlichen Lautstärken in festem zeitlichem Raster sequenziell dargeboten wurde. Der Sequenzaufbau stellte jeden Pegel jedem anderen möglichen Pegel als Vorgänger voran. Von jedem der Probanden wurden so 676 Lautheitsurteile erhoben und der statistischen Auswertung zugeführt. Probandenindividuell schwankten die Lautheitsurteile in Lage und Streuung. Mehrere Ergebnisse dieser Arbeit sind annähernd identisch mit denen einer Referenzgruppe von 26 Normalhörenden, die in einer Vorgängerarbeit mit dem gleichen Versuchsaufbau getestet worden waren. So wurden schmalbandige Stimuli signifikant leiser beurteilt als breitbandige. Beide Probandenkollektive zeigten eine positive Vorgängerpegelabhängigkeit sowie eine (signifikant stärkere) Vorgängerurteilsabhängigkeit. Sowohl bei den CI-Trägern als auch bei den Normalhörenden ging jede Erhöhung des Pegels um 5 dB mit einer signifikanten Erhöhung des Lautheitsurteils einher (strenge Monotonität). Die Lautheitsempfindungskurve der CI-Träger über alle Probanden und Stimuli verlief kontinuierlich unterhalb der der Normalhörenden. So wurde bei Sprachlautstärke (60–70 dB) gleiche Lautheit in der CI-Gruppe im Vergleich zur Referenzgruppe bei ca. 5 dB höheren Pegeln empfunden. Die unterschiedliche Lautheitsempfindung ist hinreichend durch die binaurale Hörsituation der Normalhörenden im Gegensatz zur monauralen der CI-Gruppe zu erklären. Es muss angenommen werden, dass die getesteten CI-Träger mit mindestens sechs Anpasssitzungen vor der Versuchsteilnahme über ausreichend Erfahrung zur Festlegung ihrer individuellen, idealen Lautstärke für den Alltagsgebrauch verfügten und diese an der Sprachlautstärke orientierten. Es bleibt Gegenstand weiterer Untersuchungen, warum unilaterale CI-Träger trotz der technischen Möglichkeit im Rahmen der Anpasssitzungen keine Kompensation des Lautheitsunterschiedes wünschen. / To investigate the overall level of loudness perception of cochlear implant (CI) users, 26 unilaterally implanted subjects (Med-El C40+ with Tempo+-processor) performed loudness scaling tasks. Four different types of stimuli, two narrow band and two broad band signals (1 kHz pure tone, warble tone, CCITT speech spectrum noise and a speech signal of 1 s duration each) were presented at 13 different SPLs in 5 db steps from 30 dB to 90 dB. The stimuli were presented in free field condition in an anechoic chamber. Each stimulus type was presented 169 times. This main sequence of SPLs was designed such, that each was offered 13 times and each SPL preceded each possible other. An additional initial sequence of SPLs, unrecognized by the subject, preceded the main sequence to allow for possible adaptation. Loudness judgments were made on a 1 to 50 scale, which was subdivided into five main loudness categories. Responses had to be given within a time window of four seconds. Depending on the individual CI user, loudness judgments varied in overall level and variance. In group statistics, judgments were strictly monotonic increasing with SPL, where each step of 5 dB was accompanied by a statistically significant increase in loudness judgment. Broad band stimuli were judged significantly louder than narrow band stimuli. A positive correlation of judgments both with the preceding SPL and the preceding judgment was found. In comparison to a reference group of 26 normal hearing listeners tested in the same setup in a preliminary work, the 26 CI users exhibited surprisingly similar results except for overall loudness level, especially in the lower SPL region. Generally, stimuli were judged significantly quieter than by normal hearing listeners. To produce the same loudness perception as in normal hearing listeners, approximately 5 dB higher SPLs would be necessary. The difference in loudness perception of the two groups can possibly be attributed to binaural loudness summation in normal hearing listeners as opposed to monaural hearing in the CI group. In the course of repeated mapping sessions and by adjusting their clinical processors, CI users have the option to decide about their CI system's loudness level. Assuming that binaural normal hearing establishes the optimal loudness perception, the question remains open, why CI users do not request loudness adjustment.

Les connexions entre les cellules sensorielles et les neurones primaires de l’oreille interne, appelées synapses sont essentielles à l’encodage et la transmission des informations auditives et vestibulaires vers le cerveau. C’est aussi une zone extrêmement exposée et fragile qui semble impliquée dans de nombreuses atteintes de l’audition et de l’équilibration, mais également au cours du vieillissement. Des récupérations spontanées de l’audition et de l’équilibre ont été observées suite à ces différentes atteintes chez l’Homme. Dans le cadre de ma thèse, j’ai étudié d’une part, comment des atteintes sélectives de ces synapses pouvaient générer des troubles de l’oreille interne chez l’animal, et d’autre part, comment des mécanismes de réparation spontanée de ces synapses supportent la récupération des fonctions auditives et vestibulaires. Nous avons constaté qu’il existe une hétérogénéité dans les capacités de réparations synaptiques entre la cochlée et le vestibule. L’étude des mécanismes moléculaires mis en jeu dans cette réparation synaptique pourrait ouvrir la voie au développement de nouvelles stratégies thérapeutiques pour les atteintes de l’oreille interne. / Inner ear connections between primary neurons and sensory cells, called synapses are essential for encoding and transmitting auditory and vestibular information to the brain. It is also an extremely exposed and fragile area that is involved in many hearing and balance disorders, but also during aging. Spontaneous hearing and balance recoveries have been observed following these different injuries in humans. In the context of my thesis, I studied, on the one hand, how selective lesions of these synapses could generate inner ear disorders in animals, and on the other hand, how spontaneous repair mechanisms of these synapses support auditory and vestibular functions recovery. We found that there is heterogeneity in synaptic repair capabilities between the cochlea and the vestibule. The study of the molecular mechanisms involved in this synaptic repair could pave the way for the development of new therapeutic strategies against various inner ear disorders.

Os animais com sensibilidade audiogênica, Wistar Audiogenic Rats (WAR) são modelos experimentais utilizados em pesquisas sobre audição, integração sensório-motora e epilepsias, entre elas as crises audiogênicas. O modelo de estimulação sonora repetida conhecido como kindling ou abrasamento audiogênico mimetiza um tipo de epilepsia parcial com envolvimento de estruturas límbicas. É também um modelo genético de grande importância para o estudo das epilepsias porque retrata crises em animais com seleção genética controlada. O objetivo desse estudo foi investigar as alterações morfológicas e funcionais em células ciliadas internas e externas da orelha interna em animais da cepa WAR submetidos ao abrasamento audiogênico comparando-os com animais controle. Foram utilizados 40 animais com idade de 80 a 120 dias. Os animais selecionados foram divididos em quatro grupos de estudo. Foram utilizados os animais que apresentaram função coclear normal, avaliada através do reflexo de Preyer, emissões otoacústicas por produtos de distorção (EOAPD) e limiar eletrofisiológico medido pelos potenciais evocados auditivos de tronco encefálico (PEATE). A avaliação funcional foi realizada antes do primeiro estímulo acústico e imediatamente após o último estímulo acústico. Em seguida foi realizada perfusão intracardíaca, os animais tiveram suas bulas removidas e as cócleas processadas para microscopia eletrônica de varredura. Em relação às EOAPD, os animais do grupo WAR-kindling apresentaram diferença significativa na relação sinal-ruído, sendo que animais WAR pré-kindling possuem valores significativamente superiores aos do pós-kindling. Em relação ao PEATE houve uma diferença significativa, o grupo WAR-kindling apresentou limiares com valores significativamente superiores aos do grupo Wistar kindling. Por microscopia eletrônica de varredura nos animais da cepa WAR observou-se uma estrutura irregular nos feixes de estereocílios das células ciliadas internas (CCI) e células ciliadas externas (CCE). Os exames para avaliação auditiva funcional (EOAPD), eletrofisiológica (PEATE) associados à microscopia eletrônica de varredura permitiram caracterizar as alterações morfológicas e funcionais em CCI e CCE da orelha interna em animais com sensibilidade audiogênica da cepa WAR como potenciais sequelas do abrasamento audiogênico. Os presentes dados confirmam a hipótese de que o abrasamento audiogênico na cepa WAR provoca impacto funcional e morfológico da orelha interna. / Animals of the Wistar Audiogenic Rat (WAR) strain are used as experimental models in research of auditory function, sensorimotor integration and epilepsy studies, including audiogenic seizures. The model of repeated acoustic stimulation mimics temporal lobe partial epilepsy with involvement of limbic structures and is of great importance to the study of epilepsy because it portrays a genetically selected strain. The objective of this study was to investigate the morphological and functional changes in inner and outer hair cells of the inner ear in the WAR strain after exposure to repeated acoustic stimulation and compared to control animals. 40 animals from 80 to 120 days old were included. The animals were divided into four groups of study. The animals used were those with normal cochlear function, evaluated through the Preyer Reflex, otoacoustic emissions by distortion product (DPOAE) and electrophysiological threshold measured by brainstem auditory evoked potentials (ABR). The functional assessment was performed before the first acoustic stimulus and immediately after the last acoustic stimulus. Then was performed intracardiac perfusion, the animals had their bullae removed and cochleas were processed for scanning electron microscopy. In relation to the DPOAE, the animals of the group WAR-kindling showed a significant difference in the signal-to-noise ratio, with WAR pre-kindling animals having values significantly higher than those of the post-kindling group. In relation to ABR there was a significant difference, the WAR-kindling group presented values significantly higher than those in the Wistar kindling group. By scanning electron microscopy in WAR they were observed irregular structural bundles of stereocilia of Outer Hair Cells (OHC) and Inner Hair Cells (IHC). The tests for assessing auditory function by means of DPOAE and electrophysiology (ABR) associated with the scanning electron microscopy allowed to characterize the morphological and functional changes in internal and external hair cells of the inner ear in animals with acoustic stimulation in WAR after audiogenic kindling. The present data confirm the hypothesis that kindling in WAR causes functional impact and morphological alterations in the inner ear.

Yao Jun. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Os animais com sensibilidade audiogênica, Wistar Audiogenic Rats (WAR) são modelos experimentais utilizados em pesquisas sobre audição, integração sensório-motora e epilepsias, entre elas as crises audiogênicas. O modelo de estimulação sonora repetida conhecido como kindling ou abrasamento audiogênico mimetiza um tipo de epilepsia parcial com envolvimento de estruturas límbicas. É também um modelo genético de grande importância para o estudo das epilepsias porque retrata crises em animais com seleção genética controlada. O objetivo desse estudo foi investigar as alterações morfológicas e funcionais em células ciliadas internas e externas da orelha interna em animais da cepa WAR submetidos ao abrasamento audiogênico comparando-os com animais controle. Foram utilizados 40 animais com idade de 80 a 120 dias. Os animais selecionados foram divididos em quatro grupos de estudo. Foram utilizados os animais que apresentaram função coclear normal, avaliada através do reflexo de Preyer, emissões otoacústicas por produtos de distorção (EOAPD) e limiar eletrofisiológico medido pelos potenciais evocados auditivos de tronco encefálico (PEATE). A avaliação funcional foi realizada antes do primeiro estímulo acústico e imediatamente após o último estímulo acústico. Em seguida foi realizada perfusão intracardíaca, os animais tiveram suas bulas removidas e as cócleas processadas para microscopia eletrônica de varredura. Em relação às EOAPD, os animais do grupo WAR-kindling apresentaram diferença significativa na relação sinal-ruído, sendo que animais WAR pré-kindling possuem valores significativamente superiores aos do pós-kindling. Em relação ao PEATE houve uma diferença significativa, o grupo WAR-kindling apresentou limiares com valores significativamente superiores aos do grupo Wistar kindling. Por microscopia eletrônica de varredura nos animais da cepa WAR observou-se uma estrutura irregular nos feixes de estereocílios das células ciliadas internas (CCI) e células ciliadas externas (CCE). Os exames para avaliação auditiva funcional (EOAPD), eletrofisiológica (PEATE) associados à microscopia eletrônica de varredura permitiram caracterizar as alterações morfológicas e funcionais em CCI e CCE da orelha interna em animais com sensibilidade audiogênica da cepa WAR como potenciais sequelas do abrasamento audiogênico. Os presentes dados confirmam a hipótese de que o abrasamento audiogênico na cepa WAR provoca impacto funcional e morfológico da orelha interna. / Animals of the Wistar Audiogenic Rat (WAR) strain are used as experimental models in research of auditory function, sensorimotor integration and epilepsy studies, including audiogenic seizures. The model of repeated acoustic stimulation mimics temporal lobe partial epilepsy with involvement of limbic structures and is of great importance to the study of epilepsy because it portrays a genetically selected strain. The objective of this study was to investigate the morphological and functional changes in inner and outer hair cells of the inner ear in the WAR strain after exposure to repeated acoustic stimulation and compared to control animals. 40 animals from 80 to 120 days old were included. The animals were divided into four groups of study. The animals used were those with normal cochlear function, evaluated through the Preyer Reflex, otoacoustic emissions by distortion product (DPOAE) and electrophysiological threshold measured by brainstem auditory evoked potentials (ABR). The functional assessment was performed before the first acoustic stimulus and immediately after the last acoustic stimulus. Then was performed intracardiac perfusion, the animals had their bullae removed and cochleas were processed for scanning electron microscopy. In relation to the DPOAE, the animals of the group WAR-kindling showed a significant difference in the signal-to-noise ratio, with WAR pre-kindling animals having values significantly higher than those of the post-kindling group. In relation to ABR there was a significant difference, the WAR-kindling group presented values significantly higher than those in the Wistar kindling group. By scanning electron microscopy in WAR they were observed irregular structural bundles of stereocilia of Outer Hair Cells (OHC) and Inner Hair Cells (IHC). The tests for assessing auditory function by means of DPOAE and electrophysiology (ABR) associated with the scanning electron microscopy allowed to characterize the morphological and functional changes in internal and external hair cells of the inner ear in animals with acoustic stimulation in WAR after audiogenic kindling. The present data confirm the hypothesis that kindling in WAR causes functional impact and morphological alterations in the inner ear.

In Würzburg wird seit 1997 ein Hörscreening unter Verwendung akustisch evozierter Potentiale durchgeführt. Der zu Anfang verwendete Click-Reiz wurde im März 2006 durch den auf dem Cochlea-Modell beruhenden Chirp-Reiz ersetzt. Für diesen Reiz werden auf Grund der Kompensation der Wanderwellenverzögerung der Cochlea größere Potentialamplituden beschrieben. Für diese Arbeit wurden die akustisch evozierten Potentiale von 96 Neugeborenen mit dem Maico-MB11-BERAphon aufgezeichnet. Ausgewertet und verglichen wurden die bei 40 dB HL und 60 dB HL mittels Click und Chirp generierten Potentiale I, III und V hinsichtlich ihrer Auswertbarkeit sowie ihrer Latenzzeiten und Amplitudenwerte. Besonderes Interesse galt den Latenzzeiten des Chirp und dabei der Fragestellung, in wie weit sich die Reizstruktur des Chirps in einer Verkürzung der Latenzzeiten auswirken würde. Die Ergebnisse zeigen, dass der Chirp im Vergleich zum Click zu einer deutlichen Verkürzung der Latenzen der akustisch evozierten Potentiale führt. Bei allen untersuchten Potentialen ergaben sich beim Chirp kürzere mittlere Latenzen als beim Click. Die Unterschiede erwiesen sich als statistisch signifikant. Der Chirp bewirkt eine Vergrößerung der Antwort-Amplituden. Die Mittelwerte aller Amplituden waren bei Verwendung des Chirp-Reizes größer. Eine Verbesserung der Auswertbarkeit wurde für alle untersuchten Potentiale I, III und V nachgewiesen. Zusammenfassend lässt sich feststellen, dass nach Chirp-Reizung die einzelnen Wellen der akustisch evozierten Potentiale also deutlicher, mit größerer Amplitude und mit kürzerer Latenz zur Darstellung kommen als nach Click-Reizung. Die in dieser Untersuchung im Standard-BERA-Verfahren ermittelten Unterschiede zwischen den Reizen Click und Chirp unterstreichen die Vorteile des Chirp auch für den Einsatz beim Hörscreening und der Hörschwellenbestimmung. Die durch diesen Reiz evozierte Potentialantwort führt bei kürzeren Messzeiten zu deutlich zuverlässigeren Ergebnissen, was eine Verbesserung der Qualität der Hörschwellenbestimmung und der Hörscreening-Untersuchung darstellt. / Since 1997 there is a Hearingscreening established in Wuerzburg which is based on auditory evoked potenials. In March 2006 the formerly used click-stimulus was substituted by a chirp-stimulus based on the cochlea-model. For this stimulus larger amplitudes of the potentials are discribed due to a compensation of travelling wave delay. For this study the auditory evoked potentials of 96 newborns were recorded with the Maico-MB11-BERAphon. Potentials I, III and V were evaluated and compared in terms of evaluability as well as latency and amplitude values. The latencies of the chirp-stimulus and the question, to which extent the structure of the chirp-stimulus would result in a reduction of latency times were of main interest. The results show that compared to the click the chirp-stimulus causes a clear shortening of latencies of auditory evoked potentials. For all examined potentials the chirp-stimulus showed shorter mean-latencies than the click. The differences were statistically significant. The chirp causes an increase in response amplitudes. Mean values of amplitudes were larger when using the chirp stimulus. An improvement of the evaluability was demonstrated for all investigated potentials I, III and V. In summary it can be seen that after Chirp excitation the individual waves of auditory evoked potentials occur more clearly, with greater amplitude and shorter latency than after click excitation. The differences between the click and chirp stimuli identified in these standard ABR procedures also emphasize the benefits of the chirp-stimulus for use in hearing screening and the defining of hearing thresholds. The potential response evoked by this stimulus leads to more reliable results implying significantly shorter measuring times and thus improves the quality of the defining of hearing thresholds and hearing screening examination.

La perte auditive est le trouble sensoriel le plus commun avec 40 % des personnes de plus de 65 ans affectées, entraînant, chez ces patients une dégradation de leur qualité de vie et un isolement sociale. Les principales causes sont le vieillissement ou l'exposition au bruit, mais les mutations génétiques sont aussi à l'origine de déficits auditifs. Parmi ces surdités, le Syndrome de Chudley McCullough (CMCS) est une maladie rare caractérisée par une surdité sévère et précoce associée à des anomalies cérébrales (Chudley et al., 1997). Récemment, des mutations du gène GPSM2 (G protein signaling modulator 2) ont été décrites comme étant responsables de cette pathologie sans que l'on en connaisse les mécanismes (Walsh et al., 2010). A l'aide d'un modèle d'étude murin de cette pathologie, nous avons identifié les bases moléculaires de la pathologie ainsi qu’une nouvelle fonction moléculaire pour Gpsm2 sur la modulation du cytosquelette d’actine. La perturbation de cette fonction affect à la fois la maturation des cellules auditives et la croissance des jeunes neurones, pouvant expliquer les surdités et l’hypoplasie du corps calleux décrits chez ces patients (Mauriac et al., 2017). De plus, nous avons identifié les partenaires de Gpsm2, les protéines Gαi, comme indispensables à la fonction auditive (Beer-Hammer et al., 2018). Au niveau moléculaire, nous avons découvert une nouvelle interaction de Gpsm2 avec une protéine essentielle à la maturation des cellules auditives et impliquées dans les surdités de type Usher, la Whirlin.Par conséquent, notre étude a permis de clarifier l’étiologie du CMCS et de montrer que sa complexité et son aspect multisyndromique sont dus au rôle multifonctionnel du complexe Gpsm2/G⍺i non seulement sur la dynamique de la tubuline dans des cellules en prolifération et en post-mitotiques (Ezan et al., 2013), mais aussi sur la dynamique d’actine (Mauriac et al., 2017). / Hearing loss is the most common sensory disorder, affecting 40% of people over 65 years old, leading for these patients, to the deterioration of their quality of life and to their social isolation. The main causes are aging or exposure to noise. However, many genes can also cause deafness. Among these deafnesses, the Chudley McCullough Syndrome (CMCS) is a rare disease characterized by severe and early deafness associated with brain abnormalities (Chudley et al., 1997). Recently, mutations in the GPSM2 (G protein signaling modulator 2) gene were found to be causative of this pathology, but the molecular basis were unknown (Walsh et al., 2010). Using a murine model of this pathology, we identified the molecular basis of this pathology as well as a new molecular function for Gpsm2 on the modulation of actin cytoskeleton. The disruption of this function leads to defect of the maturation of auditory hair cells and the reduction of the outgrowth of young neurons which may explain the deafness and the hypoplasia of the corpus callosum described in these patients (Mauriac et al., 2017). In addition, we identified partners of Gpsm2, Gαi proteins, as essential for auditory function (Beer-Hammer et al., 2018). At the molecular level, we have discovered a new interaction of Gpsm2 with a protein essential for the maturation of auditory cells and involved in Usher type deafness, Whirlin.Therefore, our study clarified the etiology of CMCS and show that the complexity and multisyndromic aspect of this pathology is due to the multifunctional role of the complex Gpsm2/G⍺i not only on tubulin dynamics in proliferating cells and post-mitotic cells (Ezan et al., 2013), but also on actin dynamics (Mauriac et al., 2017).