The presynaptic ribbon maintains vesicle populations at the hair cell afferent fiber synapse

  1. Lars Becker
  2. Michael E Schnee
  3. Mamiko Niwa
  4. Willy Sun
  5. Stephan Maxeiner
  6. Sara Talaei
  7. Bechara Kachar
  8. Mark A Rutherford
  9. Anthony J Ricci  Is a corresponding author
  1. Stanford University, United States
  2. National Institute of Deafness and Communicative Disorders, United States
  3. University of the Saarland, Germany
  4. Washington University at St. Louis, United States

Abstract

The ribbon is the structural hallmark of cochlear inner hair cell (IHC) afferent synapses, yet its role in information transfer to spiral ganglion neurons (SGNs) remains unclear. We investigated the ribbon's contribution to IHC synapse formation and function using KO mice lacking RIBEYE. Despite loss of the entire ribbon structure, synapses retained their spatiotemporal development and KO mice had a mild hearing deficit. IHCs of KO had fewer synaptic vesicles and reduced exocytosis in response to brief depolarization; high stimulus level rescued exocytosis in KO. SGNs exhibited a lack of sustained excitatory postsynaptic currents (EPSCs). We observed larger postsynaptic glutamate receptor plaques, potentially in compensation for the reduced EPSC rate in KO. Surprisingly, large amplitude EPSCs were maintained in KO, while a small population of low amplitude slower EPSCs was increased in number. The ribbon facilitates signal transduction at physiological stimulus levels by retaining a larger residency pool of synaptic vesicles.

Article and author information

Author details

  1. Lars Becker

    Department of Otolaryngology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Michael E Schnee

    Department of Otolaryngology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Mamiko Niwa

    Department of Otolaryngology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Willy Sun

    National Institute of Deafness and Communicative Disorders, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Stephan Maxeiner

    Institute for Anatomy and Cell Biology, University of the Saarland, Homburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Sara Talaei

    Department of Otolaryngology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Bechara Kachar

    National Institute of Deafness and Communicative Disorders, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Mark A Rutherford

    Department of Otolaryngology, Washington University at St. Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Anthony J Ricci

    Department of Otolaryngology, Stanford University, Stanford, United States
    For correspondence
    aricci@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1706-8904

Funding

National Institutes of Health (DC009913)

  • Anthony J Ricci

Action on Hearing Loss

  • Mark A Rutherford

National Institutes of Health (DC014712)

  • Mark A Rutherford

National Institutes of Health (DC013721)

  • Mamiko Niwa

National Institutes of Health (P30 44992)

  • Anthony J Ricci

National Institutes of Health (Z01-DC000002)

  • Willy Sun
  • Bechara Kachar

National Institutes of Health (ZIC DC000081)

  • Willy Sun
  • Bechara Kachar

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol 14345 of Stanford University. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of Minnesota. All auditory measurements were performed under Ketamine (100mg/kg) and Xylazine,(10mg/kg) and every effort was made to minimize suffering.

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 3,773
    views
  • 546
    downloads
  • 69
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Lars Becker
  2. Michael E Schnee
  3. Mamiko Niwa
  4. Willy Sun
  5. Stephan Maxeiner
  6. Sara Talaei
  7. Bechara Kachar
  8. Mark A Rutherford
  9. Anthony J Ricci
(2018)
The presynaptic ribbon maintains vesicle populations at the hair cell afferent fiber synapse
eLife 7:e30241.
https://doi.org/10.7554/eLife.30241

Share this article

https://doi.org/10.7554/eLife.30241

Further reading

    1. Neuroscience
    Franziska Auer, Katherine Nardone ... David Schoppik
    Research Article

    Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions to posture. However, the combined complexity of terrestrial locomotion and the rodent cerebellum motivate new approaches to perturb cerebellar function in simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) to describe the role of Purkinje cells — the output neurons of the cerebellar cortex — as larval zebrafish swam freely in depth. We achieved both bidirectional control (activation and ablation) of Purkinje cells while performing quantitative high-throughput assessment of posture and locomotion. Activation modified postural control in the pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs. Postural disruption was more widespread in older larvae, offering a window into emergent roles for the developing cerebellum in the control of posture. Finally, we found that activity in Purkinje cells could individually and collectively encode tilt direction, a key feature of postural control neurons. Our findings delineate an expected role for the cerebellum in postural control and vestibular sensation in larval zebrafish, establishing the validity of TRPV1/capsaicin-mediated perturbations in a simple, genetically tractable vertebrate. Moreover, by comparing the contributions of Purkinje cell ablations to posture in time, we uncover signatures of emerging cerebellar control of posture across early development. This work takes a major step towards understanding an ancestral role of the cerebellum in regulating postural maturation.

    1. Neuroscience
    Gáspár Oláh, Rajmund Lákovics ... Gábor Tamás
    Research Article

    Human-specific cognitive abilities depend on information processing in the cerebral cortex, where the neurons are significantly larger and their processes longer and sparser compared to rodents. We found that, in synaptically connected layer 2/3 pyramidal cells (L2/3 PCs), the delay in signal propagation from soma to soma is similar in humans and rodents. To compensate for the longer processes of neurons, membrane potential changes in human axons and/or dendrites must propagate faster. Axonal and dendritic recordings show that the propagation speed of action potentials (APs) is similar in human and rat axons, but the forward propagation of excitatory postsynaptic potentials (EPSPs) and the backward propagation of APs are 26 and 47% faster in human dendrites, respectively. Experimentally-based detailed biophysical models have shown that the key factor responsible for the accelerated EPSP propagation in human cortical dendrites is the large conductance load imposed at the soma by the large basal dendritic tree. Additionally, larger dendritic diameters and differences in cable and ion channel properties in humans contribute to enhanced signal propagation. Our integrative experimental and modeling study provides new insights into the scaling rules that help maintain information processing speed albeit the large and sparse neurons in the human cortex.