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

Moser, Tobias; Karagulyan, Nare; Neef, Jakob; Jaime Tobón, Lina María

doi:10.15252/embj.2023114587

Cited by 13 publications

(11 citation statements)

References 130 publications

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“…Intensity information is encoded by the number and types of SGNs that are activated in the cochlea. The Ia, Ib, and Ic molecular subtypes defined in mouse 39,40,42 broadly correspond to the anatomically and physiologically defined subtypes described across species 41,94 . We find that the majority of inputs onto octopus cells come from Ia ANFs, which most closely correspond to the low-threshold, high-spontaneous rate population.…”

Section: Discussionmentioning

confidence: 60%

An Anatomical and Physiological Basis for Flexible Coincidence Detection in the Auditory System

Kreeger,

Honnuraiah,

Maeker

et al. 2024

Preprint

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SummaryCoincidence detection is a common neural computation that identifies co-occurring stimuli by integration of inputs. In the auditory system, octopus cells act as coincidence detectors for complex sounds that include both synchronous and sequenced combinations of frequencies. Octopus cells must detect coincidence on both the millisecond and submillisecond time scale, unlike the average neuron, which integrates inputs over time on the order of tens of milliseconds. Here, we show that octopus cell computations in the cell body are shaped by inhibition in the dendrites, which adjusts the strength and timing of incoming signals to achieve submillisecond acuity. This mechanism is crucial for the fundamental process of integrating the synchronized frequencies of natural auditory signals over time.

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Section: Discussionmentioning

confidence: 60%

An Anatomical and Physiological Basis for Flexible Coincidence Detection in the Auditory System

Kreeger,

Honnuraiah,

Maeker

et al. 2024

Preprint

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“…Further analysis demonstrated that c-Maf and Mafb are also expressed differentially across SGN subtypes during synaptogenesis, which occurs during the first two postnatal weeks of life in mice (Coate et al, 2019; Moser et al, 2023). To mark developing SGN subtypes definitively, we used NetrinG1 Cre/+ , which selectively marks adult Ib and Ic subtypes when combined with the Ai14 Cre-dependent tdTomato reporter (RCL-tdT), consistent with its scRNA-seq expression profile ( Figure 4B ).…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, genetically labeled Ia/Ib SGNs show extensive variability in their firing rates (Siebald et al, 2023), possibly due to differences in their local connectivity. Indeed, individual IHC-SGN synaptic structures show extensive heterogeneity in composition, size, and morphology, and in presynaptic calcium channel density (Hu et al, 2020; Liberman et al, 2011; Liberman and Liberman, 2016; Michanski et al, 2019; Moser et al, 2023; Payne et al, 2021). Some of these differences are linked to subtype identity.…”

Section: Introductionmentioning

confidence: 99%

Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons

Bastille,

Lee,

Moncada-Reid

et al. 2023

Preprint

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Diverse types of synapses transmit the vast information encoded in the nervous system. Even neurons of the same type can exhibit synaptic heterogeneity that alters circuit output. For instance, in the auditory system, each inner hair cell (IHC) signals to multiple Type I spiral ganglion neurons (SGNs) via glutamatergic synapses with heterogeneous properties, thereby communicating information about the frequency, timing, and intensity of the sounds we hear. Type I SGNs fall into three molecularly distinct subtypes (Ia, Ib and Ic) that make synapses with predictable differences in the position and volume of the glutamate receptor puncta, as well as the size of the apposing pre-synaptic ribbon in the IHC. To define the intrinsic mechanisms that determine subtype-appropriate synaptic properties, we investigated Maf family transcription factors, which play known roles in synapse development. Loss of c-Maf or Mafb from SGNs led to opposing effects on synaptic morphology and auditory responses, whereas loss of both c-Maf and Mafb led to formation of dysmorphic synapses and abnormal auditory responses. Further, although c-Maf and Mafb are both expressed in all SGNs, their levels differ across SGN subtypes. Single-cell RNA sequencing of single mutant SGNs revealed that c-Maf and Mafb have both shared and unique effects on subtype-specific programs of gene expression, including molecules associated with synaptic function and neuronal excitability. Double mutant SGNs, on the other hand, failed to diversify and showed dramatic changes in gene expression that included genes not changed in either single mutant. Together, these findings suggest that a combinatorial code of c-Maf and Mafb acts across SGN subtypes to establish synaptic heterogeneity that is critical for normal hearing function.

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“…This applied to the synthetic ribbons as well as to the AZ-like clusters of Bassoon, RBP2 and Ca V 1.3 Ca 2+ channels. However, all three components exhibited variability beyond the substantial natural heterogeneity found among the IHC AZs (Moser et al , 2023). Functionally, Bassoon and RBP2 co-expression resulted in larger whole-cell Ca V 1.3 currents.…”

Section: Discussionmentioning

confidence: 99%

Establishing synthetic ribbon-type active zones in a heterologous expression system

Kapoor,

Schwenzer,

Dresbach

et al. 2024

Preprint

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Encoding of several sensory modalities into neural signals is mediated by ribbon synapses. The synaptic ribbon tethers synaptic vesicles at the presynaptic active zone (AZ) and might act as a super-scaffold organizing AZ topography. Here we employed a synthetic biology approach to reconstitute ribbon-type AZs in HEK293 cells for probing their minimal molecular requirements and studying presynaptic Ca2+ channel clustering. Co-expressing a membrane-targeted version of the AZ-protein Bassoon and the ribbon core protein RIBEYE, we observed structures recapitulating basic aspects of ribbon-type AZs, which we call synthetic ribbons or SyRibbons. SyRibbons with Ca2+ channel clusters formed upon additional expression of CaV1.3 Ca2+ channels and RIM-binding protein 2 (RBP2), known to promote presynaptic Ca2+ channel clustering. Confocal and super-resolution microscopy along with functional analysis by patch-clamp and Ca2+-imaging revealed striking similarities and interesting differences of SyRibbons in comparison to native IHC ribbon-type AZs. In summary, we identify Ca2+ channels, RBP, membrane-anchored Bassoon, and RIBEYE as minimal components for reconstituting a basic ribbon-type AZ. SyRibbons might complement animal studies on molecular interactions of AZ proteins.

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

Cited by 13 publications

References 130 publications

An Anatomical and Physiological Basis for Flexible Coincidence Detection in the Auditory System

An Anatomical and Physiological Basis for Flexible Coincidence Detection in the Auditory System

Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons

Establishing synthetic ribbon-type active zones in a heterologous expression system

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