1. Neuroscience
Download icon

Mapping the human subcortical auditory system using histology, post mortem MRI and in vivo MRI at 7T

  1. Kevin R Sitek  Is a corresponding author
  2. Omer Faruk Gulban  Is a corresponding author
  3. Evan Calabrese
  4. G Allan Johnson
  5. Agustin Lage-Castellanos
  6. Michelle Moerel
  7. Satrajit S Ghosh
  8. Federico de Martino
  1. Massachusetts Institute of Technology, United States
  2. Maastricht University, Netherlands
  3. Duke University, United States
Tools and Resources
  • Cited 9
  • Views 2,188
  • Annotations
Cite this article as: eLife 2019;8:e48932 doi: 10.7554/eLife.48932

Abstract

Studying the human subcortical auditory system non-invasively is challenging due to its small, densely packed structures deep within the brain. Additionally, the elaborate three-dimensional (3-D) structure of the system can be difficult to understand based on currently available 2-D schematics and animal models. We addressed these issues using a combination of histological data, post mortem magnetic resonance imaging (MRI), and in vivo MRI at 7 Tesla. We created anatomical atlases based on state-of-the-art human histology (BigBrain) and post mortem MRI (50 μm). We measured functional MRI (fMRI) responses to natural sounds and demonstrate that the functional localization of subcortical structures is reliable within individual participants who were scanned in two different experiments. Further, a group functional atlas derived from the functional data locates these structures with a median distance below 2mm. Using diffusion MRI tractography, we revealed structural connectivity maps of the human subcortical auditory pathway both in vivo (1050 μm isotropic resolution) and post mortem (200 μm isotropic resolution). This work captures current MRI capabilities for investigating the human subcortical auditory system, describes challenges that remain, and contributes novel, openly available data, atlases, and tools for researching the human auditory system.

Article and author information

Author details

  1. Kevin R Sitek

    McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, United States
    For correspondence
    ksitek@mit.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2172-5786
  2. Omer Faruk Gulban

    Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
    For correspondence
    faruk.gulban@maastrichtuniversity.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7761-3727
  3. Evan Calabrese

    Center for In Vivo Microscopy, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. G Allan Johnson

    Center for In Vivo Microscopy, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Agustin Lage-Castellanos

    Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Michelle Moerel

    Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Satrajit S Ghosh

    McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5312-6729
  8. Federico de Martino

    Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

Funding

NWO (864-13-012)

  • Omer Faruk Gulban
  • Federico de Martino

National Institutes of Health (5R01EB020740)

  • Satrajit S Ghosh

National Institutes of Health (P41EB019936)

  • Satrajit S Ghosh

National Institutes of Health (5F31DC015695)

  • Kevin R Sitek

Eaton Peabody Laboratory at Mass Eye and Ear (Amelia Peabody Scholarship)

  • Kevin R Sitek

Harvard Brain Science Initiative (Travel Grant)

  • Kevin R Sitek

National Institutes of Health (P41EB015897)

  • G Allan Johnson

National Institutes of Health (1S10OD010683-01)

  • G Allan Johnson

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

Ethics

Human subjects: The experimental procedures were approved by the ethics committee of the Faculty for Psychology and Neuroscience at Maastricht University (reference number: ERCPN-167_09_05_2016), and were performed in accordance with the approved guidelines and the Declaration of Helsinki. Written informed consent was obtained for every participant before conducting the experiments. All participants reported to have normal hearing, had no history of hearing disorder/impairments or neurological disease.

Reviewing Editor

  1. Jonathan Erik Peelle, Washington University in St. Louis, United States

Publication history

  1. Received: May 30, 2019
  2. Accepted: July 28, 2019
  3. Accepted Manuscript published: August 1, 2019 (version 1)
  4. Version of Record published: August 23, 2019 (version 2)

Copyright

© 2019, Sitek 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

  • 2,188
    Page views
  • 306
    Downloads
  • 9
    Citations

Article citation count generated by polling the highest count across the following sources: PubMed Central, Crossref, Scopus.

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)

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

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

Further reading

    1. Neuroscience
    Reeba Susan Jacob et al.
    Short Report Updated

    The Parkinson’s disease protein α-synuclein (αSyn) promotes membrane fusion and fission by interacting with various negatively charged phospholipids. Despite postulated roles in endocytosis and exocytosis, plasma membrane (PM) interactions of αSyn are poorly understood. Here, we show that phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3), two highly acidic components of inner PM leaflets, mediate PM localization of endogenous pools of αSyn in A2780, HeLa, SK-MEL-2, and differentiated and undifferentiated neuronal SH-SY5Y cells. We demonstrate that αSyn binds to reconstituted PIP2 membranes in a helical conformation in vitro and that PIP2 synthesizing kinases and hydrolyzing phosphatases reversibly redistribute αSyn in cells. We further delineate that αSyn-PM targeting follows phosphoinositide-3 kinase (PI3K)-dependent changes of cellular PIP2 and PIP3 levels, which collectively suggests that phosphatidylinositol polyphosphates contribute to αSyn’s function(s) at the plasma membrane.

    1. Cell Biology
    2. Neuroscience
    Javier Emperador-Melero et al.
    Research Advance

    It has long been proposed that Leukocyte common Antigen-Related Receptor Protein Tyrosine Phosphatases (LAR-RPTPs) are cell-adhesion proteins that control synapse assembly. Their synaptic nanoscale localization, however, is not established, and synapse fine structure after knockout of the three vertebrate LAR-RPTPs (PTPδ, PTPσ and LAR) has not been tested. Here, superresolution microscopy reveals that PTPδ localizes to the synaptic cleft precisely apposed to postsynaptic scaffolds of excitatory and inhibitory synapses. We next assessed synapse structure in newly generated triple-conditional knockout mice for PTPδ, PTPσ and LAR, complementing a recent independent study of synapse function after LAR-RPTP ablation (Sclip and Südhof, 2020). While mild effects on synaptic vesicle clustering and active zone architecture were detected, synapse numbers and their overall structure were unaffected, membrane anchoring of the active zone persisted, and vesicle docking and release were normal. Hence, despite their localization at synaptic appositions, LAR-RPTPs are dispensable for presynapse structure and function.