A novel class of inferior colliculus principal neurons labeled in vasoactive intestinal peptide-cre mice

  1. David Goyer
  2. Marina Augusto Silveira
  3. Alexander P George
  4. Nichole L Beebe
  5. Ryan M Edelbrock
  6. Peter T Malinski
  7. Brett R Schofield
  8. Michael Thomas Roberts  Is a corresponding author
  1. University of Michigan, United States
  2. Northeast Ohio Medical University, United States

Abstract

Located in the midbrain, the inferior colliculus (IC) is the hub of the central auditory system. Although the IC plays important roles in speech processing, sound localization, and other auditory computations, the organization of the IC microcircuitry remains largely unknown. Using a multifaceted approach in mice, we have identified vasoactive intestinal peptide (VIP) neurons as a novel class of IC principal neurons. VIP neurons are glutamatergic stellate cells with sustained firing patterns. Their extensive axons project to long-range targets including the auditory thalamus, auditory brainstem, superior colliculus, and periaqueductal gray. Using optogenetic circuit mapping, we found that VIP neurons integrate input from the contralateral IC and the dorsal cochlear nucleus. The dorsal cochlear nucleus also drove feedforward inhibition to VIP neurons, indicating that inhibitory circuits within the IC shape the temporal integration of ascending inputs. Thus, VIP neurons are well-positioned to influence auditory computations in a number of brain regions.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 3, 4, 5, 7, and 8 and Table 2.

Article and author information

Author details

  1. David Goyer

    Kresge Hearing Research Institute, Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Marina Augusto Silveira

    Kresge Hearing Research Institute, Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Alexander P George

    Kresge Hearing Research Institute, Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Nichole L Beebe

    Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ryan M Edelbrock

    Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Peter T Malinski

    Kresge Hearing Research Institute, Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Brett R Schofield

    Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0875-7759
  8. Michael Thomas Roberts

    Kresge Hearing Research Institute, Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, United States
    For correspondence
    microb@umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2835-8752

Funding

Deutsche Forschungsgemeinschaft (401540516)

  • David Goyer

Hearing Health Foundation (Emerging Research Grant)

  • Michael Thomas Roberts

National Institutes of Health (DC016880)

  • Michael Thomas Roberts

National Institutes of Health (DC004391)

  • Brett R Schofield

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

Ethics

Animal experimentation: All experiments were approved by the University of Michigan Institutional Animal Care and Use Committee (protocol # PRO00006642 and PRO00008773) and were in accordance with NIH guidelines for the care and use of laboratory animals.

Copyright

© 2019, Goyer et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,572
    views
  • 498
    downloads
  • 40
    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. David Goyer
  2. Marina Augusto Silveira
  3. Alexander P George
  4. Nichole L Beebe
  5. Ryan M Edelbrock
  6. Peter T Malinski
  7. Brett R Schofield
  8. Michael Thomas Roberts
(2019)
A novel class of inferior colliculus principal neurons labeled in vasoactive intestinal peptide-cre mice
eLife 8:e43770.
https://doi.org/10.7554/eLife.43770

Share this article

https://doi.org/10.7554/eLife.43770

Further reading

    1. Neuroscience
    Charles R Heller, Gregory R Hamersky, Stephen V David
    Research Article

    Categorical sensory representations are critical for many behaviors, including speech perception. In the auditory system, categorical information is thought to arise hierarchically, becoming increasingly prominent in higher-order cortical regions. The neural mechanisms that support this robust and flexible computation remain poorly understood. Here, we studied sound representations in the ferret primary and non-primary auditory cortex while animals engaged in a challenging sound discrimination task. Population-level decoding of simultaneously recorded single neurons revealed that task engagement caused categorical sound representations to emerge in non-primary auditory cortex. In primary auditory cortex, task engagement caused a general enhancement of sound decoding that was not specific to task-relevant categories. These findings are consistent with mixed selectivity models of neural disentanglement, in which early sensory regions build an overcomplete representation of the world and allow neurons in downstream brain regions to flexibly and selectively read out behaviorally relevant, categorical information.

    1. Neuroscience
    2. Stem Cells and Regenerative Medicine
    Amber R Philp, Carolina R Reyes ... Francisco J Rivera
    Short Report

    Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiation in vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis (Calr+/-), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS.