Patterned pre-sensory spontaneous activity drives the structural refinement of developing cochlear ribbon synapses.

Overview

1. Auditory Neuroscience Group, Institute of Physiology, Medical University Innsbruck, Innsbruck, Austria
2. Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Goettingen, Goettingen, Germany
3. CavX – Calcium Channels in Excitable Cells PhD Program, Medical University Innsbruck, Innsbruck, Austria
4. Department of Otolaryngology, Head and Neck Surgery, University Medical Center Goettingen, Goettingen, Germany
5. Collaborative Research Centre 889 ‘Cellular Mechanisms of Sensory Processing’, Goettingen, Germany
6. Intas Science Imaging Instruments GmbH, Goettingen, Germany

Abstract

Introduction: In the mammalian cochlea, hearing relies on highly specialized ribbon-type synapses between sensory inner hair cells (IHCs) and postsynaptic spiral ganglion neurons. During early postnatal maturation, structural and functional refinements re-shape synaptic morphology and thereby maximize release efficiency in the run-up to hearing onset. This developmental period is further characterized by the occurrence of pre-sensory spontaneous activity waves, which are essential for the functional maturation of the ascending auditory pathway– yet, their importance for IHC presynaptic structural refinement remains uncertain.

Methods: To investigate activity-dependent structural plasticity at cochlear ribbon synapses, we combined genetic, pharmacological, and optogenetic approaches with immunohistochemical and electrophysiological analyses. Moreover, we developed a novel optical stimulation device (OSD) that enables millisecond-precise, long-term and differentially-patterned optogenetic activation of cochlear IHCs under tightly controlled conditions within a standard tissue culture incubator.

Results: Using this experimental framework, we show that positive as well as negative activity modulation triggers dynamic and rapidly-inducible homeostatic scaling of ribbon synapse morphology. Moreover, our data indicate that the temporal pattern of the presynaptic activity acts as a fundamental regulatory component of this process.

Discussion: Our results suggest that – prior to hearing onset – pre-sensory synaptic activity plays a critical role in shaping cochlear ribbon synapse architecture in the developing auditory system.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data and to no code of its authors: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

• doi:10.17632/fkxph7grn5.1, at the source; found in “Data availability statement”

Data availability statement

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author. All relevant source data are deposited on Mendeley Data for public access (Mendeley Data, doi: 10.17632/fkxph7grn5.1 (https://doi.org./10.17632/fkxph7grn5.1)).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 11 authors, 6 keywords, 2 funders, 72 references.

Cite

This paper

Halim, V. C., Hallbrucker, L., Ahrend, J. F., Setz, C., Voorn, R. A., Franke, S., Konrad, V., Seiler, A., Pangršič, T., Roesler, S., & Vogl, C. (2026). Patterned pre-sensory spontaneous activity drives the structural refinement of developing cochlear ribbon synapses. Frontiers in synaptic neuroscience, 18, 1730181. https://doi.org/10.3389/fnsyn.2026.1730181

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1126/sciadv.ady4344

Charting the nanotopography of inner hair cell synapses using MINFLUX nanoscopy.

Journal: Science advances

In common: cellular / molecular, 22 references

[2] doi:10.1126/sciadv.ady8532

Structure and function of otoferlin, a synaptic protein of sensory hair cells essential for hearing.

Journal: Science advances

In common: cellular / molecular, 13 references

[3] doi:10.7554/elife.98254 [code]

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

Journal: eLife

In common: cellular / molecular, 12 references

[4] doi:10.1038/s41467-024-55519-w [code]

In vivo spontaneous Ca<sup>2+</sup> activity in the pre-hearing mammalian cochlea.

Journal: Nature communications

In common: cellular / molecular, 12 references

[5] doi:10.1073/pnas.2315599121 [code]

Auditory hair cells and spiral ganglion neurons regenerate synapses with refined release properties in vitro.

Journal: Proceedings of the National Academy of Sciences of the United States of America

In common: cellular / molecular, 12 references

[6] doi:10.1016/j.celrep.2022.111649 [code]

Developmental spontaneous activity promotes formation of sensory domains, frequency tuning and proper gain in central auditory circuits.

Journal: Cell reports

In common: 10 references

[7] doi:10.1113/ep093267 [code]

Spontaneous Ca<sup>2+</sup> signals in the developing mammalian cochlea of live mice under different anaesthetic regimes.

Journal: Experimental physiology

In common: cellular / molecular, 8 references

[8] doi:10.1016/j.isci.2024.108825 [code]

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

Journal: iScience

In common: cellular / molecular, 8 references

[9] doi:10.1371/journal.pbio.3002160 [code]

Preservation of developmental spontaneous activity enables early auditory system maturation in deaf mice.

Journal: PLoS biology

In common: 8 references

[10] doi:10.1016/j.celrep.2024.114025

BAI1 localizes AMPA receptors at the cochlear afferent post-synaptic density and is essential for hearing.

Journal: Cell reports

In common: cellular / molecular, 7 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: code errors and mismatches between the code and the paper about this paper and its code, from readers and its authors, beside the paper and its tracing map.

Reproductions: reports from readers who ran the authors' code and did not get the paper's result, what they ran, with which environment, commit and data.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.