Diversity matters — extending sound intensity coding by inner hair cells via heterogeneous synapses

The EMBO Journal, Год журнала: 2023, Номер 42(23)

Опубликована: Окт. 6, 2023

Abstract Our sense of hearing enables the processing stimuli that differ in sound pressure by more than six orders magnitude. How to process a wide range stimulus intensities with temporal precision is an enigmatic phenomenon auditory system. Downstream dynamic compression active cochlear micromechanics, inner hair cells (IHCs) cover full intensity input. Yet, firing rate each their postsynaptic spiral ganglion neurons (SGNs) encodes only fraction it. As population, respective individual coding fractions entire audible range. such “dynamic fractionation” arises topic current research and focus this review. Here, we discuss mechanisms for generating diverse functional properties SGNs formulate testable hypotheses. We postulate interplay synaptic heterogeneity, molecularly distinct subtypes SGNs, efferent modulation serves neural decomposition information thus contributes population code intensity.

Язык: Английский

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Spatial patterns of noise-induced inner hair cell ribbon loss in the mouse mid-cochlea

iScience, Год журнала: 2024, Номер 27(2), С. 108825 - 108825

Опубликована: Янв. 8, 2024

In the mammalian cochlea, moderate acoustic overexposure leads to loss of ribbon-type synapse between inner hair cell (IHC) and its postsynaptic spiral ganglion neuron (SGN), causing a reduced dynamic range hearing but not permanent threshold elevation. A prevailing view is that such ribbon (known as synaptopathy) selectively impacts low-spontaneous-rate high-threshold SGN fibers contacting predominantly modiolar IHC face. However, spatial pattern synaptopathy remains scarcely characterized in most sensitive mid-cochlear region, where two morphological subtypes with distinct size gradients coexist. Here, we used volume electron microscopy investigate noise exposure-related changes mouse IHCs without loss. Our quantifications reveal differ worst-hit area synaptopathy. Moreover, show relative enrichment mitochondria surviving terminals, providing key experimental evidence for long-proposed role SGN-terminal synaptic vulnerability.

Язык: Английский

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Toward Optogenetic Hearing Restoration

Annual Review of Neuroscience, Год журнала: 2024, Номер 47(1), С. 103 - 121

Опубликована: Апрель 10, 2024

The cochlear implant (CI) is considered the most successful neuroprosthesis as it enables speech comprehension in majority of million otherwise deaf patients. In hearing by electrical stimulation auditory nerve, broad spread current from each electrode acts a bottleneck that limits transfer sound frequency information. Hence, there remains major unmet medical need for improving quality with CIs. Recently, optogenetic cochlea has been suggested an alternative approach restoration. Cochlear optogenetics promises to more information, hence hearing, light can conveniently be confined space activate nerve within smaller tonotopic ranges. this review, we discuss latest experimental and technological developments restoration outline remaining challenges en route clinical translation.

Язык: Английский

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Flexible auditory training, psychophysics, and enrichment of common marmosets with an automated, touchscreen-based system

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Март 28, 2022

Devising new and more efficient protocols to analyze the phenotypes of non-human primates, as well their complex nervous systems, is rapidly becoming paramount importance. This because with genome-editing techniques, recently adopted animal models for fundamental translational research have been established. One aspect in particular, namely cognitive hearing, has difficult assess compared visual cognition. To address this, we devised autonomous, standardized, unsupervised training testing auditory capabilities common marmosets a cage-based standalone, wireless system. All tested voluntarily operated device on daily basis went from naïve experienced at own pace ease. Through series experiments, here show, that animals autonomously learn associate sounds images; flexibly discriminate sounds, detect varying loudness. The developed platform principles combine in-cage psychoacoustic assessment an enriched environment does not rely dietary restriction or social separation, compliance 3Rs principle.

Язык: Английский

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Multiscale photonic imaging of the native and implanted cochlea

Proceedings of the National Academy of Sciences, Год журнала: 2021, Номер 118(18)

Опубликована: Апрель 26, 2021

The cochlea of our auditory system is an intricate structure deeply embedded in the temporal bone. Compared with other sensory organs such as eye, has remained poorly accessible for investigation, example, by imaging. This limitation also concerns further development technology restoring hearing case cochlear dysfunction, which requires quantitative information on spatial dimensions and sensorineural status cochlea. Here, we employed X-ray phase-contrast tomography light-sheet fluorescence microscopy their combination multiscale multimodal imaging morphology species that serve established animal models research. We provide a systematic reference morphological parameters relevant implant rodent nonhuman primate models. simulate spread light from emitters optical implants within reconstructed cochlea, indicates spatially narrow optogenetic excitation spiral ganglion neurons.

Язык: Английский

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Models of Cochlea Used in Cochlear Implant Research: A Review

Annals of Biomedical Engineering, Год журнала: 2023, Номер 51(7), С. 1390 - 1407

Опубликована: Апрель 22, 2023

Abstract As the first clinically translated machine-neural interface, cochlear implants (CI) have demonstrated much success in providing hearing to those with severe profound loss. Despite their clinical effectiveness, key drawbacks such as damage, partly from insertion forces that arise during implantation, and current spread, which limits focussing ability, prevent wider CI eligibility. In this review, we provide an overview of anatomical physical properties cochlea a resource aid development accurate models improve future treatments. We highlight advancements various physical, animal, tissue engineering, computational need for models, challenges use, perspective on directions.

Язык: Английский

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3D virtual histology of rodent and primate cochleae with multi-scale phase-contrast X-ray tomography

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 7, 2025

Multi-scale X-ray phase contrast tomography (XPCT) enables three-dimensional (3D), non-destructive imaging of intact small animal cochlea and apical cochlear turns. Here we report on post-mortem excised non-human primate rodent cochleae at different [Formula: see text]-CT nano-CT synchrotron instruments. We explore sample embeddings, stainings regimes. Under optimized conditions preparation, instrumentation, protocol, retrieval, high image quality detail level can be achieved in 3D reconstructions. The showcased instrumentation protocols along with the reconstucted volumes serve as benchmarks reference for multi-scale microanatomy histology. provided this work cover a wide range scales are intended augmented tools auditory research.

Язык: Английский

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3D imaging of the human temporal bone by X-ray phase-contrast tomography

npj Imaging, Год журнала: 2025, Номер 3(1)

Опубликована: Май 20, 2025

Abstract Studying the subtle and intricate three-dimensional structure of human cochlea embedded in temporal bone requires structure-preserving imaging approaches with adaptable field view resolution. Synchrotron X-ray phase-contrast tomography at novel beamline BM18 (EBS, ESRF) offers unique capability to achieve histological resolution scale entire organ, based on high lateral coherence, long propagation distances, optimized spectral range. At same time advances laboratory μ -CT instrumentation protocols also open up new opportunities for 3D micro-anatomy histopathology, including reconstruction nerve tissue when suitable staining are used. Here we report post mortem bones excised cochleae, both unstained stained visualize auditory nerve. Further, highlight use this modality development cochlear implant technology.

Язык: Английский

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Volumetric atlas of the rat inner ear from microCT and iDISCO+ cleared temporal bones

PeerJ, Год журнала: 2025, Номер 13, С. e19512 - e19512

Опубликована: Май 26, 2025

Background Volumetric atlases are an invaluable tool in neuroscience and otolaryngology, greatly aiding experiment planning surgical interventions, as well the interpretation of experimental clinical data. The rat is a major animal model for hearing balance studies, detailed volumetric atlas central auditory system (Waxholm) available. However, Waxholm only contains low-resolution inner ear featuring five structures. In present work, we segmented annotated 34 structures ear, yielding which can be integrated with brain atlas. Methods We performed iodine-enhanced microCT iDISCO+-based clearing fluorescence lightsheet microscopy imaging on sample temporal bones. Image stacks were semiautomated way, volumes reconstructed from samples. Using geometrical morphometry, high-resolution segmentations obtained registered into coordinate Results Cleared autofluorescence was used reconstruction most structures, including fluid-filled compartments, nerves sensory epithelia, blood vessels, connective tissue resolution allowed thin ducts (reuniting, saccular endolymphatic), utriculoendolymphatic valve. vestibulocochlear artery coursing through bone found to associated reuniting duct, visible both cleared samples, thus allowing infer duct location scans. labyrinths showed minimal shape distortions, shown by alignment labyrinths. membranous could display variable collapse superior division, especially roof canal ampullae, whereas inferior division (saccule cochlea) preserved, exception Reissner’s membrane that ruptures second cochlear turn. As example use, separate macrophage populations spiral ganglion, neuron dendrites, Organ Corti. Conclusion have bone, available image printable 3D objects shared repository download. These teaching, localizing cells or other features within modeling vestibular physiology training automated segmentation machine learning tools.

Язык: Английский

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Model-based prediction of optogenetic sound encoding in the human cochlea by future optical cochlear implants

Computational and Structural Biotechnology Journal, Год журнала: 2022, Номер 20, С. 3621 - 3629

Опубликована: Янв. 1, 2022

When hearing fails, electrical cochlear implants (eCIs) partially restore by direct stimulation of spiral ganglion neurons (SGNs). As light can be better confined in space than current, optical CIs (oCIs) provide more spectral information promising a fundamental improvement restoration implants. Here, we turned to computer modelling for predicting the outcome optogenetic future oCIs humans. We combined three-dimensional reconstruction human cochlea with ray-tracing simulation emission from LED or laser-coupled waveguide emitters oCI. Irradiance was read out at somata SGNs. The irradiance values reached waveguides were about 14 times higher LEDs, same radiant flux emitter. Moreover, outperformed LEDs regarding selectivity. either emitter type showed greater selectivity when compared eCI. In addition, modeling effects source-to-SGN distance, orientation sources and impact scar tissue further informs development restoration.

Язык: Английский

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