Optimized Tuning of Auditory Inner Hair Cells to Encode Complex Sound through Synergistic Activity of Six Independent K+ Current Entities

Dierich, Marlen; Altoè, Alessandro; Koppelmann, Julia; Evers, Saskia; Renigunta, Vijay; Schäfer, Martin K.; Naumann, Ronald; Verhulst, Sarah; Oliver, Dominik; Leitner, Michael G.

doi:10.1016/j.celrep.2020.107869

Cited by 21 publications

(49 citation statements)

References 72 publications

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“…The genes encoding for the Kv1.8, Kv11.1 and Kv12.1 have recently been identified to contribute to I K,s in IHCs (Dierich et al . 2020). However, the characteristic signature of fully functional mature IHCs is the expression of Kcnma1 (Rüttiger et al .…”

Section: Resultsmentioning

confidence: 99%

“…One component of this K + current is carried by a delayed rectifier (I K,s ), which exhibits slow activation kinetics and seems to be derived from the immature K + current I K,neo (Marcotti et al 2004a). The genes encoding for the Kv1.8, Kv11.1 and Kv12.1 have recently been identified to contribute to I K,s in IHCs (Dierich et al 2020). However, the characteristic signature of fully functional mature IHCs is the expression of Kcnma1 (Rüttiger et al 2004) and Kcnq4 (Kubisch et al 1999).…”

Section: Ihcs Retain a Normal Basolateral Membrane Profile With Agementioning

confidence: 99%

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Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea

Jeng

Carlton

Johnson

et al. 2020

The Journal of Physiology

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Age-related hearing loss is a progressive hearing loss involving environmental and genetic factors, leading to a decrease in hearing sensitivity, threshold and speech discrimination. r We compared age-related changes in inner hair cells (IHCs) between four mouse strains with different levels of progressive hearing loss. r The surface area of apical coil IHCs (9-12 kHz cochlear region) decreases by about 30-40% with age. r The number of BK channels progressively decreases with age in the IHCs from most mouse strains, but the basolateral membrane current profile remains unchanged. r The mechanoelectrical transducer current is smaller in mice harbouring the hypomorphic Cdh23 allele Cdh23 ahl (C57BL/6J; C57BL/6NTac), but not in Cdh23-repaired mice (C57BL/6NTac Cdh23+), indicating that it could contribute to the different progression of hearing loss among mouse strains. r The degree of efferent rewiring onto aged IHCs, most likely coming from the lateral olivocochlea fibres, was correlated with hearing loss in the different mouse strains.

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Section: Resultsmentioning

confidence: 99%

Section: Ihcs Retain a Normal Basolateral Membrane Profile With Agementioning

confidence: 99%

Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea

Jeng

Carlton

Johnson

et al. 2020

The Journal of Physiology

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“…Analytical descriptions of IHC-ANF processing have evolved over the years, with the IHC transduction shifting from simplified low-pass filter implementations [13,51,56,57,59,78] to detailed models of basolateral outward K + currents [7][8][9][10]. State-of-the-art IHC-ANF models estimate the vibrations of the IHC stereocilia based on the mechanical drive to the IHC and often describe the ANF spikes or instantaneous firing rate resulting from the depletion and replenishment of different neurotransmitter stores [57,58,60,79].…”

Section: Discussionmentioning

confidence: 99%

“…In Fig. 8, simulated AC/DC ratios are compared between responses of CoNNear IHC and two other state-of-the-art IHC analytical descriptions, the Zilany et al [57] and Dierich et al [10] models. The tonal stimuli described in Methods were used as inputs to the Zilany et al cochlea-IHC model, while their extracted cochlear responses were used for the Dierich et al IHC model.…”

Section: Generalisability Of the Framework To Other Analytical Model mentioning

confidence: 99%

“…By virtue of Ca 2+ -driven exocytosis, glutamate is released to drive the synaptic transmission between the IHC and the innervated auditory-nerve fiber (ANF) synapses and neurons [38]. Experimentally extracted IHC parameters from in-vitro, wholecell patch clamp measurements of the cellular structures and channel properties [39,40] have led to different model descriptions of the nonlinear and frequency-dependent IHC transduction [10,[41][42][43]. Parameters for analytical IHC-ANF synapse models have mainly been derived from single-unit AN recordings to basic auditory stimuli in cats and small rodents [44][45][46][47][48][49][50] the function of IHC-ANF synapses over the past decades has inspired numerous analytical model descriptions of the IHC, IHC-ANF synapse and ANF neuron complex [11][12][13][51][52][53][54][55][56][57][58][59][60][61].…”

Section: Introductionmentioning

confidence: 99%

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A convolutional neural-network framework for modelling auditory sensory cells and synapses

Drakopoulos

Baby

Verhulst

2020

Preprint

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In classical computational neuroscience, transfer functions are derived from neuronal recordings to derive analytical model descriptions of neuronal processes. This approach has resulted in a variety of Hodgkin-Huxley-type neuronal models, or multi-compartment synapse models, that accurately mimic neuronal recordings and have transformed the neuroscience field. However, these analytical models are typically slow to compute due to their inclusion of dynamic and nonlinear properties of the underlying biological system. This drawback limits the extent to which these models can be integrated within large-scale neuronal simulation frameworks and hinders an uptake by the neuro-engineering field which requires fast and efficient model descriptions. To bridge this translational gap, we present a hybrid, machine-learning and computational-neuroscience approach that transforms analytical sensory neuron and synapse models into artificial-neural-network (ANN) neuronal units with the same biophysical properties. Our ANN-model architecture comprises parallel and differentiable equations that can be used for backpropagation in neuro-engineering applications, and offers a simulation run-time improvement factor of 70 and 280 on CPU or GPU systems respectively. We focussed our development on auditory sensory neurons and synapses, and show that our ANN-model architecture generalizes well to a variety of existing analytical models of different complexity. The model training and development approach we present can easily be modified for other neuron and synapse types to accelerate the development of large-scale brain networks and to open up avenues for ANN-based treatments of the pathological system.

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A versatile functional interaction between electrically silent KV subunits and KV7 potassium channels

Renigunta,

Xhaferri,

Shaikh

et al. 2024

Cell. Mol. Life Sci.

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Voltage-gated K+ (KV) channels govern K+ ion flux across cell membranes in response to changes in membrane potential. They are formed by the assembly of four subunits, typically from the same family. Electrically silent KV channels (KVS), however, are unable to conduct currents on their own. It has been assumed that these KVS must obligatorily assemble with subunits from the KV2 family into heterotetrameric channels, thereby giving rise to currents distinct from those of homomeric KV2 channels. Herein, we show that KVS subunits indeed also modulate the activity, biophysical properties and surface expression of recombinant KV7 isoforms in a subunit-specific manner. Employing co-immunoprecipitation, and proximity labelling, we unveil the spatial coexistence of KVS and KV7 within a single protein complex. Electrophysiological experiments further indicate functional interaction and probably heterotetramer formation. Finally, single-cell transcriptomic analyses identify native cell types in which this KVS and KV7 interaction may occur. Our findings demonstrate that KV cross-family interaction is much more versatile than previously thought—possibly serving nature to shape potassium conductance to the needs of individual cell types.

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Optimized Tuning of Auditory Inner Hair Cells to Encode Complex Sound through Synergistic Activity of Six Independent K+ Current Entities

Cited by 21 publications

References 72 publications

Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea

Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea

A convolutional neural-network framework for modelling auditory sensory cells and synapses

A versatile functional interaction between electrically silent KV subunits and KV7 potassium channels

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