Unter Spikelets versteht man kleine Depolarisationen mit einer Spike-ähnlichen Wellenform, die man in intrazellulären Ableitungen von verschiedenen Neuronentypen messen kann. In kortikalen Pyramidenzellen wurde ausgeprägte Spikelet-Aktivität nachgewiesen, die erheblich das Membranpotential beeinflussen kann (Crochet et al., 2004; Epsztein et al., 2010; Chorev and Brecht, 2012). Nichtsdestotrotz bleibt der Ursprung von Spikelets in diesen Neuronen unbekannt. In der vorgelegten Arbeit nutzte ich theoretische Modellierung um die Mechanismen von Spikelet-Erzeugung in Pyramidenzellen zu untersuchen. Zuerst sah ich die verschiedenen Hypothesen über den Ursprung von Spikelets durch. In der Literatur entdeckte ich zwei verschiedene Typen von Spikelets. Diese Arbeit konzentriert sich auf den häufiger vorkommenden Typ von Spikelets, welcher durch relativ große Amplituden gekennzeichnet ist. Die Eigenschaften dieser Spikelets passen am besten zu einem axonal Erzeugungsmechanismus. Im zweiten Kapitel widmete ich mich der Hypothese, dass somatische Spikelets axonalen Ursprungs mit somato-dendritischen Inputs hervorgerufen werden können. Ich identifizierte Bedingungen, die es erlauben ein Aktionspotential (AP) am Initialsegment vom Axon (AIS) zu initiieren, welches sich entlang des Axons ausbreitet, aber kein AP im Soma auslöst. Schließlich simulierte ich extrazelluläre Wellenformen von APs und Spikelets und verglich sie mit experimentellen Daten (Chorev and Brecht, 2012). Dieser Vergleich zeigte auf, dass die extrazellulären Wellenformen von Spikelets, die innerhalb einer Zellen am AIS erzeugt werden, gut zu den Daten passen. Zusammenfassend unterstützen meine Ergebnisse die Hypothese, dass Spikelets in Pyramidenzellen am AIS entstehen. Dieser Mechanismus könnte ein Mittel zum Energiesparen bei der Erzeugung von Output-APs sein. Außerdem könnte dadurch die dendritische Plastizität, die auf der Rückwärtspropagierung von APs beruht, reguliert werden. / Spikelets are transient spike-like depolarizations of small amplitudes that can be measured in somatic intracellular recordings of many neuron types. Pronounced spikelet activity has been demonstrated in cortical pyramidal neurons in vivo (Crochet et al., 2004; Epsztein et al., 2010; Chorev and Brecht, 2012), influencing membrane voltage dynamics including action potential initiation. Nevertheless, the origin of spikelets in these neurons remains elusive. In thi thesis, I used computational modeling to examine the mechanisms of spikelet generation in pyramidal neurons. First, I reviewed the hypotheses previously suggested to explain spikelet origin. I discovered two qualitatively different spikelet types described in the experimental literature. This thesis focuses on the more commonly reported spikelet type, characterized by relatively large amplitudes of up to 20 mV. I found that the properties of these spikelets fit best to an axonal generation mechanism. Second, I explored the hypothesis that somatic spikelets of axonal origin can be evoked with somato-dendritic inputs. I identified the conditions allowing these orthodromic inputs to trigger an action potential at the axon initial segment, which propagates along the axon to the postsynaptic targets, but fails to elicit an action potential in the soma and the dendrites. Third, I simulated extracellular waveforms of action potentials and spikelets and compared them to experimental data (Chorev and Brecht, 2012). This comparison demonstrated that the extracellular waveforms of single-cell spikelets of axonal origin are consistent with the data. Together, my results suggest that spikelets in pyramidal neurons might originate at the axon initial segment within a single cell. Such a mechanism might be a way of reducing the energetic costs associated with the generation of output action potentials. Moreover, it might allow to control the dendritic plasticity by backpropagating action potentials.

Este trabalho apresenta a modelagem matemática e a simulação de potenciais de ação de unidades motoras de músculos de vertebrados visando a posterior simulação do eletromiograma. Para conseguir isso, inicialmente se fez uma compilação de dados existentes para a distribuição das fibras musculares (FBs) nas unidades motoras (MUs) de vários músculos, e as modelagens matemáticas descritos na literatura para o potencial de ação de uma FB (SFAP) e de uma MU (MUAP). Com base nos dados fisiológicos, primeiro se localizou as FBs em um músculo, por meio de uma aproximação de que as FBs estão rodeadas de outras seis no músculo. Para conseguir isto se construiram hexágonos concêntricos por MU, e posteriormente se localizou as FBs nas MUs, cobrindo uma faixa entre 75 e 2000 FBs, o que corresponde a músculos distais de mamíferos. Depois se fez uma aproximação para a distribuição de 170000 FBs nas 272 MUs da cabeça medial do músculo gastrocnêmio (MG) do gato, conseguindo numa primeira simulação localizar cerca de 70% das FBs para cada MU. Com esta localização das FBs no músculo baseados nos dados da literatura se aproximaram os retardos axonais por uma distribuição gaussiana, com média de 2 ms (gato) ou 10 ms (homem) e com desvio padrão de menos de 0,5 ms, desprezando o atraso axonal nas ramificações axonais, que foi estimado no máximo 29 vezes menor. Para a geração do SFAP trabalhou-se com dois modelos, um analítico, o qual resulta em simulações numéricas demoradas, e, outro numérico baseado na convolução da corrente com uma função peso. Para o modelo numérico dobrou-se imaginariamente o comprimento das FBs, para levar em conta o erro computacional de fim de fibra. O modelo numérico resultou em um tempo de simulação 30 vezes menor que o analítico. Adicionalmente, para simular a captação externa (i.e. na pele), fez-se uma aproximação para a função que modela os eletrodos de superfície de secção circular localizados a uma distância maior que 1,79 mm das FBs, mostrando um espectro similar ao reportado na literatura. Finalmente, os MUAPs obtidos resultavam com formas de onda e espectros similares ao descrito na literatura. Além disto, em certos casos, obtiveram-se MUAPs com indentações, seja localizando as junções neuromusculares em bandas da ordem de 1 mm de espessura, seja quando o tempo de atraso axonal foi considerado junto com a velocidade de condução da FB em função da raiz quadrada do diâmetro da FB. Foram feitas simulações para os MG e bíceps braquial do homem. Neste último caso, foram obtidos MUAPs similares aos captados para pessoas saludáveis, e foi observada a freqüência de disparos dos potenciais de ação do motoneurônio no espectro do MUAP. Quanto às formas dos agrupamentos das FBs em uma MU, não se obtiveram diferenças significativas para as FBs posicionadas homogênea e aleatoriamente, exceto uma ligeira variação nas amplitudes. No entanto, ocurreu uma mudança na faixa espectral, quando as FBs estavam concentradas. / This work presents the mathematical model and simulation of motor unit action potentials of vertebrate muscles aiming at after simulation of the electromyogram. To obtain this, initially, it was made a compilation of several data about the distribution of muscle fibers (FBs) in motor units (MUs) of many muscles, and the mathematical models of the action potential of a single FB (SFAP) and MU (MUAP), reported in previous works. On the basis of this physiological data, first, the FB was located in a muscle, using an approximation in which the FBs are encircled with other six FBs in the muscle. To reach this, concentric hexagons were constructed to build the surface of the MU, and later the FBs were situated in the MU, covering a range between 75 and 2000 FBs, corresponding to mammals extremity muscles. Later, a new approximation were was madein order to distribute the 170000 FBs in the 272 MUs of the medial head of muscle medialis gastrocnemius (MG) of the cat, reaching, in a first simulation, the localization of almost 70% of the FBs at each MU. With the FBs lalready allocated in the muscle, and based in data of previous works, their axonal delay were approximated by a gaussian distribution, with mean of 2 ms (cat) or 10 ms (man) and standard deviation of less than 0,5 ms, discarding the axonal delay in the axonal branching, that were estimated to affectup to 29 times less. To SFAP generation, two models were used, the first analytical, resulting in delayed numerical simulations, and the other based on convolution of the second derivate of the current with a weight function, where the length of the FBs was imaginarily duplicated, in order to consider the end fiber effect. Using this, a simulation time 30 times lesser than the analytical one was obtained. Additionally, so as to simulate the external recording (i.e. in the skin), it was made an approximation to the function that models the circular shape surface electrodes located at distances greater than 1,79 mm of the FBs, showing a similar spectrum reported. Finally, the waves and spectrum of the simulated MUAPs resulted similar to the ones reported in the literature. Beyond this, in certain cases, MUAPs were simulated with some tuned, either locating the neuromuscular junctions with thickness bands of 1 mm, or, when the axonal delay and the FB muscle fiber conduction velocity were considered as a function of the square root fiber diameter. This was simulated for MUAPs of MG and biceps brachii muscles of human beings, in the last case it has reached the waveforms and tuned found in heath subjects, and it was visualized the mean frequency of firing rate at the spectrum. In order to know how much affects grouping for the FBs to waves a MU, they were not found significant differences with FBs located homogeneously and randomly, except a little variation in the amplitude of the MUAP. However, they presented a change in the spectral bandwidth when the FBs are more concentrated.

The recovery from prior stimulation of the compound action potential (CAP) was measured using a forward masking stimulus paradigm in four normal-hearing, human subjects. The CAP was recorded using a wick electrode placed on the tympanic membrane. The effects of a 4000-Hz, 97-dB SPL conditioning stimulus on CAP amplitude in response to a 4000-Hz probe were measured as a function of conditioner–probe interval for three probe levels. The normalized probe response amplitude was completely recovered to the control values at an average conditioner–probe interval of 1359 ms, similar to that observed in chinchilla (Relkin, E.M., Doucet, J.R., Sterns, A., 1995. Recovery of the compound action potential following prior stimulation: evidence for a slow component that reflects recovery of low spontaneous-rate auditory neurons, Hear. Res. 83, 183–189). The present results are interpreted as a consequence of the slow recovery of low spontaneous-rate (SR), high threshold neurons from prior stimulation (Relkin, E.M., Doucet, J.R., 1991. Recovery from prior stimulation. I: Relationship to spontaneous firing rates of primary auditory neurons. Hear. Res. 55, 215–222) and may provide indirect physiological evidence for the existence of a class of low-SR auditory neurons in humans.

Electrical propagation in excitable tissue, such as nerve fibers and heart muscle, is described by a nonlinear diffusion-reaction parabolic partial differential equation for the transmembrane voltage $V(x,t)$, known as the cable equation. This equation involves a highly nonlinear source term, representing the total ionic current across the membrane, governed by a Hodgkin-Huxley type ionic model, and requires the solution of a system of ordinary differential equations. Thus, the model consists of a PDE (in 1-, 2- or 3-dimensions) coupled to a system of ODEs, and it is very expensive to solve, especially in 2 and 3 dimensions. In order to solve this equation numerically, we develop an algorithm, extended from the Parareal Algorithm, to efficiently incorporate space-parallelized solvers into the framework of the Parareal algorithm, to achieve time-and-space parallelization. Numerical results and comparison of the performance of several serial, space-parallelized and time-and-space-parallelized time-stepping numerical schemes in one-dimension and in two-dimensions are also presented.

Long-term potentiation (LTP) and depression (LTD) are important forms of activity-dependent synaptic plasticity believed to play a role in memory at the cellular level. It has previously been described that synthesis of new proteins is needed to maintain LTP longer than a few hours. Other reports argue that sufficient proteins for stable LTP are already available. The present study aims to examine the role of protein synthesis in LTD, the presumed mirror mechanism of LTP. Experiments were carried out in hippocampal slices from young (12-45 days) and old (12-18 weeks) Sprague-Dawley rats. Extracellular techniques were used to study synaptic responses in the Schaffer-collateral-commissural pathway. Plasticity was induced electrically by low frequency stimulation (2-3 trains at 1 Hz for 15 min) or chemically by brief exposure to certain glutamate receptor agonists (NMDA at 20 µM for 3 min or DHPG at 100 µM for 10 min). Whole slice protein synthesis was quantified by assessing 3H-leucine incorporation. Stable LTD (> 8 h) was be obtained by either electrical or chemical activation. Protein synthesis inhibitors anisomycin (40 uM) and cycloheximide (100 uM) both failed to influence the magnitude of LTD. Moreover, no age difference was found, in terms of stable LTD in both young and old rats under inhibition of protein synthesis. The potency of the inhibitors was found to be high, depressing synthesis down to a few percent. It is concluded that sufficient proteins for generating stable LTD are normally present in the brain, implying a large safety-margin for cellular memory.

No description available.

Effective cochlear implant fitting (or programming) is essential for providing good hearing outcomes, yet it is a subjective and error-prone task. The initial objective of this research was to automate the procedure using the auditory nerve electrically evoked compound action potential (the ECAP) and machine intelligence. The Nucleus?? cochlear implant measures the ECAP via its Neural Response Telemetry (NRT™) system. AutoNRT™, a commercial intelligent system that measures ECAP thresholds with the Nucleus Freedom™ implant, was firstly developed in this research. AutoNRT uses decision tree expert systems that automatically recognise ECAPs. The algorithm approaches threshold from lower stimulus levels, ensuring recipient safety during postoperative measurements. Clinical studies have demonstrated success on approximately 95% of electrodes, measured with the same efficacy as a human expert. NRT features other than ECAP threshold, such as the ECAP recovery function, could not be measured with similar success rates, precluding further automation and loudness prediction from data mining results. Despite this outcome, a better application of the ECAP threshold profile towards fitting was established. Since C-level profiles (the contour of maximum acceptable stimulus levels across the implant array) were observed to be flatter than T-level profiles (the contour of minimum audibility), a flattening of the ECAP threshold profile was adopted when applied as a fitting profile at higher stimulus levels. Clinical benefits of this profile scaling technique were demonstrated in a 42 subject study. Data mining results also provided an insight into the ECAP recovery function and refractoriness. It is argued that the ECAP recovery function is heavily influenced by the size of the recruited neural population, with evidence gathered from a computational model of the cat auditory nerve and NRT measurements with 21 human subjects. Slower ECAP recovery, at equal loudness, is a consequence of greater neural recruitment leading to lower mean spike probabilities. This view can explain the counterintuitive association between slower ECAP recovery and greater temporal responsiveness to increasing stimulation rate. This thesis presents the first attempt at achieving completely automated cochlear implant fitting via machine intelligence; a future generation implant, capable of high fidelity auditory system measurements, may realise the ultimate objective.

Abstract Cytosolic Ca2+, [Ca2+]I , has a key role in intracellular signalling during excitation-contraction coupling (E-C coupling) in cardiac myocytes. The sarcoplasmic reticulum (SR) is a main intracellular Ca2+ store and the Na+-Ca2+ exchanger (NaCaX) is a major mechanism to extrude Ca2+ for balancing the Ca2+ influx via L-type Ca2+ channels during excitation. Furthermore, [Ca2+]I also affects the configuration of the action potential (AP). The present study, by combination of animal experiments and computer simulations, investigated the roles of [Ca2+]I, SR and NaCaX in cardiac myocytes, in Ca2+-induced Ca2+ release (CICR) and in modulation of APs. The following were studied: (I) the stretch-induced effects on rat atrium and the role of [Ca2+]I in modulation of AP; (II) the role of the SR in modulation in rat atrium by stretch; (III) the role of NaCaX; (IV) the role of [Ca2+]I in modulation of action potential duration (APD) in myocytes with short and long action potential duration. In isolated rat atrial preparations, the physiological or moderate stretch stimulus caused two- phasic rise of developed contraction, rapid and slow phases, accompanied with slow increments of [Ca2+]I and prolongations of action potentials durations in continuous recordings. In sustained stretch, the APD and [Ca2+]I were all increased significantly when intra-atrial pressure increased from 1 to 3 mmHg. In computer simulations, employing a rat atrial model (RA model), it was found that stretch-activated channels and increased Tn C affinity for Ca2+ alone could not produce the changes in the experiments. Only after both mechanisms applied to model cells, the main experimental findings could be mimicked (I). The prolongation of APD induced by stretch in rat atrial preparations was reversed after depleting the Ca2+ content of the SR by application of the SR functional inhibitors, ryanodine, thapsigargin and caffeine (II). In the computer simulation using modified guinea pig ventricular model, the Ca2+ entry via the reversal of NaCaX was found to be accounting 25% of the total activator Ca2+ for triggering Ca2+ release from the SR during normal excitation. This contribution increases with elevated [Na+]i (III). In a guinea pig ventricular model (GPV model) and a RA model were employed for investigating the regulation of APD by [Ca2+]I-dependent membrane currents. Increased SR Ca2+ content produced an elevated [Ca2+]I in both model cells, leading to prolongation of APD in the RA model but shortening in the GPV model. Increased [Ca2+]I enhances the NaCaX current in the same scale in both models, but inhibits L-type Ca current much more in the GPV model than the RA model (IV). In conclusion, (I) Stretch-induced [Ca2+]I increase prolongs the rat atrial AP by enhancing the NaCaX inward current. Stretch-activated channels (SACs) and increased affinity of TnC for Ca2+ are main general factors responsible for the variety of changes of cardiac muscles induced by stretch. (II) The SR plays a crucial role in the modulation of myocytes by accumulating the additional Ca2+ influx via sarcolemma during stretch. (III) The NaCaX contributes a small part for activator Ca2+ for calcium release from the SR during normal cardiac E-C coupling. However, this contribution is [Na]i-dependent, and in some pathological conditions, it may be a potential factor for cardiac arrhythmogenesis. (IV) Different effects on the NaCaX and L-type channels induced by increased [Ca2+]I leads to the dispersion of the change of APD in myocytes with long and short AP during inotropic interventions that increase the [Ca2+]I.

Abstract The goal of this thesis was to investigate and build new circuit solutions for electrophysiological measurements that would be used in biophysical research of nervous system and brain activity. The first aim was to build a micromotion compensation system that could compensate for the relative movement of measurement microelectrodes and neurons that can cause signal attenuation or even loss. The purpose of this work was to stabilize the microelectrode with respect to the preparation in order to achieve more stable measurements with small test animals, such as insects, rodents or reptiles. The movement is measured with a touch probe sensor and a feedback loop containing a piezoelectric actuator that adjusts the position of the electrode. A prototype micromotion compensation system was built and its performance was measured in a realistic measurement condition. The compensation system was used to reduce the motion of the probe to below 1 µm, resulting in up to 98% compensation below 10 Hz. The design of the micromotion compensation system took advantage of a preceding study on a piezoelectric bimorph actuator/sensor structure. This study is also presented in the thesis. Another aim of the research was to design and build an integrated multichannel neural signal recording system with stimulation capabilities. The circuit was designed to amplify, digitize and stream out data from extracellular neuronal signal measurements. The main target of the measurement system are action potential signals, which are a type of “digital communication” between nerve cells that evolution has produced. The waveform of these action potential signals is the focus of interest. To accomplish this measurement, the developed circuit contains preamplification, multiplexing, post-amplification, A/D conversion and control logic for the A/D converter and data transmission. The circuit is also externally programmable, and it contains DACs for tuning high-pass filter corner frequency, amplifier bias current and stimulation current. The implemented electronics have low noise, low power and small circuit area. The gain of the circuit is adjustable from 100 to 5000 and the high-pass filter corner frequency from 0.5 Hz to 900 Hz. The sample rate is 20.833 kSps and the data rate is 3.5 Mbps. The measured noise level of the circuit is 7.5μV (rms) (300 Hz - 10 kHz) and the whole chip consumes less than 2 mW of power. A 16-channel prototype chip with 0.35μm CMOS technology was manufactured and its performance was measured. Backend electronics containing a microcontroller supporting high-speed USB data transfer was also programmed for the system. The device was tested in real measurements of neuronal signals in a cockroach (Periplaneta americana) preparation, and reliable streaming of the recorded data to the PC verified its proper function. / Tiivistelmä Tämän väitöskirjatyön tavoitteena oli kehittää mittaus- ja säätöjärjestelmiä aivotutkimuksen ja biofysiikan sovelluksiin. Ensimmäisenä tutkimuskokonaisuutena oli mittaus- ja säätöjärjestelmän kehittäminen, minkä tavoitteena oli mahdollistaa aivojen sähköisen signaloinnin mittaaminen mahdollisimman luonnollisessa tilassa olevilla koe-eläimillä (esim. hyönteiset, matelijat tai pienet nisäkkäät). Tätä varten kehitettiin aktiivinen liikekompensointimekanismi, jossa kosketusanturilla mitattiin aivokudoksen mikrometriluokan mekaanista liikettä ja kompensoitiin sähköistä mittausta suorittavan anturin ja aivon välinen suhteellinen liike liikuttamalla takaisinkytkentälenkissä olevaa pietsosähköistä aktuaattoria. Kompensointimekanismin toiminta testattiin realistisissa mittausolosuhteissa. Liikekompensoinnilla saatiin vähennettyä mittausanturin liikettä suhteessa kudokseen alle mikrometriin, maksimikompensoinnin ollessa noin 98 % alle 10 Hz:n taajuudella. Väitöskirjaan liitettiin pietsosähköisiin komponentteihin liittyen taustatiedoksi artikkeli aiemmin suunnitellusta pietsosähköisestä bimorph aktuaattori/sensori -komponentista. Toisen tutkimuskokonaisuuden muodosti suurten hermosolupopulaatioiden toiminnan mittaamiseen sekä stimulointiin kehitetty monikanavainen järjestelmä. Tärkeimpänä mittauskohteena työssä ovat ekstrasellulaariset aktiopotentiaalisignaalit, jotka ovat eräänlainen evoluution tuottama “digitaalinen” hermosolujen välinen kommunikaatiomenetelmä. Kiinnostuksen kohteena ovat näiden aktiopotentiaalisignaalien aaltomuodot. Mittauksia varten työssä kehitettiin hermosolujen solun ulkopuoliseen nesteeseen asetettaviin elektrodeihin kytkettävä elektroniikka, jolla pystytään sekä stimuloimaan että mittaamaan jokaista elektrodia. Suunniteltu vahvistinelektroniikka on matalakohinainen, matalatehoinen ja pienikokoinen. Mittausjärjestelmään on suunniteltu myös multipleksointi, A/D-muunninelektroniikka sekä ohjauslogiikka, joka sisältää muunnostulosten puskuroinnin integroidun piirin rekisteripankkeihin, SPI-liitynnän high-speed USB protokollaa tukevalle mikrokontrollerille sekä konfiguraatiorekistereitä, joihin SPI-väylän kautta kirjoittamalla voidaan säätää piirin vahvistusta, operaatiovahvistimien biasvirtoja, kaistanleveyttä sekä stimulaatiovirtojen voimakkuuksia. Piirin vahvistus on säädettävissä 100:n ja 5000:n välillä ja ylipäästösuodatuksen kulmataajuus välillä 0,5 Hz - 900 Hz. Piirin näytteistystaajuus on 20,833 kSps ja tiedonsiirtonopeus 3,5 Mbps. Piirin kohinatasoksi mitattiin 7,5 µV (rms) (300 Hz - 10 kHz) ja koko piirin tehonkulutukseksi alle 2 mW. Integroidusta piiristä valmistettiin 16-kanavainen prototyyppi 0,35 µm:n CMOS-teknologialla. Kehitetyn laitteen toiminta varmistettiin mittaamalla hermosignaaleja torakkapreparaatista (Periplaneta americana). Mittausdata siirrettiin onnistuneesti ja luotettavasti PC:lle.

Contexte: La réponse synchrone des fibres auditives, évaluée à partir de l'onde I des potentiels d'action évoqués auditifs (PEA), ou à partir du potentiel d'action composite (PAC) du nerf auditif, est l'élément clé du dépistage des neuropathies auditives. De récentes études ont toutefois montré que le seuil et l'amplitude de cette réponse pouvaient être absolument normaux malgré une perte importante de fibres du nerf auditif. Dans ce travail de thèse, nous proposons une nouvelle méthode d'exploration fonctionnelle, potentiellement applicable à l'homme, rendant mieux compte du nombre et de l'intégrité des fibres du nerf auditif. Cette méthode a été évaluée à l'aide d'un modèle pharmacologique de neuropathie physiologiquement pertinent.Matériel et méthodes: Chez des gerbilles, une perte sélective de fibres auditives a été induite par application d'une faible concentration d'ouabaïne dans la niche de la fenêtre ronde de la cochlée. Cette neuropathie a ensuite été caractérisée par des comptages de synapses (immunohistochimie/imagerie confocale 3D) et l'enregistrement de l'activité unitaire de fibres du nerf auditif. Les PAC et l'activité soutenue du nerf ont été enregistrés 6 jours après l'application d'ouabaïne, à l'aide d'une électrode de recueil disposée dans la niche de la fenêtre ronde. Résultats: L'application d'ouabaïne induit une perte spécifique des fibres à basse activité spontanée (AS<0,5 potentiel d'action/sec) comme observé au cours du vieillissement et après une surexposition sonore. La disparition de cette population de fibres est indétectable à l'aide du PAC car leur réponse unitaire est à la fois retardée et désynchronisée. Par contre, l'amplitude de la réponse soutenue du nerf se révèle être un bien meilleur indicateur de la perte des fibres à basse activité spontanée. Pour aller plus loin, nous avons mis au point une méthode qui permet d'observer l'activité synchrone et soutenue du nerf auditif dans une même réponse. Cette approche rend compte des trois mécanismes de fusion vésiculaire (libération rapide, lente et soutenue) de la première synapse auditive.Conclusion: L'analyse de la réponse soutenue du nerf auditif est une approche fiable pour déterminer le nombre et le phénotype fonctionnel des fibres qui composent le nerf auditif. Cette méthode, applicable à l'homme, devrait améliorer le dépistage des neuropathies, avec une meilleure différenciation des atteintes d'origine synaptique et/ou neuronale.Mots clés: Cochlée, nerf auditif, potentiel d'action composite, activité soutenue du nerf auditif, enregistrement unitaires, ouabaïne, neuropathie / Background: The synchronous activation of the auditory nerve fibers (ANFs), is commonly studied through the compound action potential (CAP), or the auditory brainstem responses (ABR), to probe deafness in experimental and clinical settings. Recent studies have shown that substantial ANF loss can coexist with normal hearing threshold, and even unchanged CAP amplitude, making the detection of auditory neuropathies difficult. In this study, we took advantage of the round window neural noise (RWNN) to probe ANF loss in a physiologically-relevant model of neuropathy.Material and methods: ANF loss was induced by the application of ouabain onto the round window niche. CAP and RWNN of the gerbil's cochlea were recorded through an electrode placed onto the round window niche, 6 days after the ouabain application. Afferent synapse counts and single-unit recordings were carried-out to determine the degree and the nature of ANF loss, respectively. Results: Application of a low ouabain-dose into the gerbil RW niche elicits a specific degeneration of low spontaneous rate (SR) fibers, as shown by single-unit recordings. Simultaneous recordings (CAP/single-unit) demonstrate that low-SR fibers have a weak contribution to the CAP amplitude because of their delayed and broad first spike latency distribution. However, the RWNN amplitude decreases with the degree of synaptic loss. The RWNN method is therefore more sensitive than CAP to detect low-SR fiber loss, most probably because it reflects the sustained discharge rate of ANFs. Based on these data, we proposed a far-field method (Peri-stimulus time response-PSTR) to assess the fast, slow, and sustain vesicular release at the first auditory synapse.Conclusion: The round window neural noise is a faithful proxy to probe the degree and the SR-based nature of fiber loss. This method could be translated into the clinic to probe hidden hearing loss and orient the practitioner toward synaptopathy and/or neuropathy.Key words: Cochlea, auditory nerve, compound action potential, round window neural noise, single fiber recording, ouabain-induced neuropathy