Noise-Induced Synaptopathy Impacts the Long and Short Sensory Hair Cells Differently in the Mammalian Cochlea DOI
Yan Lu, Jing Liu, Bei Li

et al.

Published: Jan. 1, 2023

In the mammalian cochlea, moderate acoustic overexposure leads to irreversible loss of ribbon-type synapse between sensory inner hair cell (IHC) and its postsynaptic auditory nerve fiber (ANF), causing a reduced dynamic range hearing but not permanently-elevated threshold. A prevailing view is that such ribbon (known as synaptopathy) selectively impacts those low-spontaneous-rate high-threshold ANFs contacting predominantly modiolar face IHCs. However, spatial pattern synaptopathy remains scarce in most sensitive mid-cochlear region, where long short IHCs with distinct size gradients coexist. Here, we used volume electron microscopy investigate noise exposure-related changes mouse without loss. Our quantifications reveal worst-hit areas are pillar Moreover, show relative enrichment mitochondrial content survived ANF terminals, providing key experimental evidence for long-proposed role mitochondria selective degeneration following insult.

Language: Английский

Diversity matters — extending sound intensity coding by inner hair cells via heterogeneous synapses DOI Creative Commons
Tobias Moser,

Nare Karagulyan,

Jakob Neef

et al.

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(23)

Published: Oct. 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.

Language: Английский

Citations

41
Spatial patterns of noise-induced inner hair cell ribbon loss in the mouse mid-cochlea DOI Creative Commons
Yan Lu, Jing Liu, Bei Li

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(2), P. 108825 - 108825

Published: Jan. 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.

Language: Английский

Citations

9
Toward Optogenetic Hearing Restoration DOI
Antoine Huet, Thomas Mager, Christian Goßler

et al.

Annual Review of Neuroscience, Journal Year: 2024, Volume and Issue: 47(1), P. 103 - 121

Published: April 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.

Language: Английский

Citations

6
Flexible auditory training, psychophysics, and enrichment of common marmosets with an automated, touchscreen-based system DOI Creative Commons
Antonino Calapai, Jorge Cabrera-Moreno, Tobias Moser

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: March 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.

Language: Английский

Citations

23
Multiscale photonic imaging of the native and implanted cochlea DOI Open Access
Daniel Keppeler, Christoph A. Kampshoff, Anupriya Thirumalai

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(18)

Published: April 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.

Language: Английский

Citations

29
Models of Cochlea Used in Cochlear Implant Research: A Review DOI Creative Commons
Filip Hrnčiřík, Iwan Roberts,

Ilkem Sevgili

et al.

Annals of Biomedical Engineering, Journal Year: 2023, Volume and Issue: 51(7), P. 1390 - 1407

Published: April 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.

Language: Английский

Citations

11
3D virtual histology of rodent and primate cochleae with multi-scale phase-contrast X-ray tomography DOI Creative Commons
Jannis Schaeper, Christoph A. Kampshoff, Bettina Wolf

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 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.

Language: Английский

Citations

0
Model-based prediction of optogenetic sound encoding in the human cochlea by future optical cochlear implants DOI Creative Commons
Lakshay Khurana, Daniel Keppeler, Lukasz Jablonski

et al.

Computational and Structural Biotechnology Journal, Journal Year: 2022, Volume and Issue: 20, P. 3621 - 3629

Published: Jan. 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.

Language: Английский

Citations

13
Ontogeny of cellular organization and LGR5 expression in porcine cochlea revealed using tissue clearing and 3D imaging DOI Creative Commons
Adele Moatti, Chen Li, Sasank Sivadanam

et al.

iScience, Journal Year: 2022, Volume and Issue: 25(8), P. 104695 - 104695

Published: June 30, 2022

Over 11% of the world's population experience hearing loss. Although there are promising studies to restore in rodent models, size, ontogeny, genetics, and frequency range most rodents' cochlea do not match that humans. The porcine can bridge this gap as it shares many anatomical, physiological, genetic similarities with its human counterpart. Here, we provide a detailed methodology process image 3D using tissue clearing light-sheet microscopy. resulting images be employed compare cochleae across different ages conditions, investigate ontogeny cochlear cytoarchitecture, produce quantitative expression maps LGR5, marker progenitors mice. These data reveal hair cell organization, inner ear morphology, cellular cartography organ Corti, spatiotemporal LGR5 dynamic over developmental stages pattern previously documented.

Language: Английский

Citations

10
On the Fabrication and Characterization of Polymer-Based Waveguide Probes for Use in Future Optical Cochlear Implants DOI Open Access
Christian Helke,

M. Reinhardt,

Markus Arnold

et al.

Materials, Journal Year: 2022, Volume and Issue: 16(1), P. 106 - 106

Published: Dec. 22, 2022

Improved hearing restoration by cochlear implants (CI) is expected optical (oCI) exciting optogenetically modified spiral ganglion neurons (SGNs) via an pulse generated outside the cochlea. The guided to SGNs inside cochlea flexible polymer-based waveguide probes. fabrication of these probes realized using 6" wafer-level micromachining processes, including lithography processes such as spin-coating cladding layers and a layer in between etch for structuring layer. Further adhesion metal laser diode (LD) bonding light-outcoupling structures are also integrated this process flow. Optical microscope SEM images revealed that majority waveguides sufficiently smooth guide light with low intensity loss. By coupling into detecting outcoupled from waveguide, we distinguished losses caused bending outcoupling. were used first modules called single-beam guides (SBGs) based on probe, ball lens LD. Finally, SBGs tested animal models proof-of-concept implantation experiments.

Language: Английский

Citations

10