Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves

Abstract

Spontaneous slow oscillation-associated slow wave activity represents an internally generated state which is characterized by alternations of network quiescence and stereotypical episodes of neuronal activity - slow wave events. However, it remains unclear which macroscopic signal is related to these active periods of the slow wave rhythm. We used optic fiber-based calcium recordings of local neural populations in cortex and thalamus to detect neurophysiologically defined slow calcium waves in isoflurane anesthetized rats. The individual slow wave events were used for an event-related analysis of simultaneously acquired whole-brain BOLD fMRI. We identified BOLD responses directly related to onsets of slow calcium waves, revealing a cortex-wide BOLD correlate: the entire cortex was engaged in this specific type of slow wave activity. These findings demonstrate a direct relation of defined neurophysiological events to a specific BOLD activity pattern and were confirmed for ongoing slow wave activity by independent component and seed-based analyses.

Article and author information

Author details

  1. Miriam Schwalm

    Focus Program translational Neurosciences and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg-University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Florian Schmid

    Department of Clinical Radiology, University Hospital Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Lydia Wachsmuth

    Department of Clinical Radiology, University Hospital Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Hendrik Backhaus

    Focus Program translational Neurosciences and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg-University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Andrea Kronfeld

    Focus Program translational Neurosciences and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg-University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Felipe Aedo Jury

    Focus Program translational Neurosciences and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg-University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Pierre-Hugues Prouvot

    Focus Program translational Neurosciences and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg-University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Consuelo Fois

    Focus Program translational Neurosciences and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg-University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Franziska Albers

    Department of Clinical Radiology, University Hospital Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Timo van Alst

    Department of Clinical Radiology, University Hospital Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Cornelius Faber

    Department of Clinical Radiology, University Hospital Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7683-7710
  12. Albrecht Stroh

    Focus Program translational Neurosciences and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg-University Mainz, Mainz, Germany
    For correspondence
    albrecht.stroh@unimedizin-mainz.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9410-4086

Funding

Deutsche Forschungsgemeinschaft (Fa474/5)

  • Cornelius Faber

Deutsche Forschungsgemeinschaft (SFB 1080)

  • Albrecht Stroh

Deutsche Forschungsgemeinschaft (SFB 1193)

  • Albrecht Stroh

Deutsche Forschungsgemeinschaft (SPP 1665)

  • Albrecht Stroh

Focus Program translational Neurosciences

  • Miriam Schwalm
  • Albrecht Stroh

Interdisciplinary Center for Clinical Research Münster (Fa3/1603,PIX)

  • Cornelius Faber

Excellence Cluster Cells in Motion (EXEC 1003)

  • Cornelius Faber

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

Reviewing Editor

  1. Jan-Marino Ramirez, Seattle Children's Research Institute and University of Washington, United States

Ethics

Animal experimentation: Animal husbandry and experimental manipulation were carried out according to animal welfare guidelines of the Westfalian Wilhelms-University and the Johannes Gutenberg-University Mainz and were approved by the Landesamt für Natur-, Verbraucher- und Umweltschutz Nordrhein-Westfalen, Recklinghausen, Germany (animal protocol number: 84-02.04.2015.A427), and the Landesuntersuchungsamt Rheinland-Pfalz, Koblenz, Germany (animal protocol number: G 14-1-040). All surgery was performed under deep isoflurane anesthesia.

Version history

  1. Received: April 7, 2017
  2. Accepted: September 14, 2017
  3. Accepted Manuscript published: September 15, 2017 (version 1)
  4. Accepted Manuscript updated: September 19, 2017 (version 2)
  5. Version of Record published: October 26, 2017 (version 3)

Copyright

© 2017, Schwalm 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

  • 4,153
    views
  • 729
    downloads
  • 76
    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. Miriam Schwalm
  2. Florian Schmid
  3. Lydia Wachsmuth
  4. Hendrik Backhaus
  5. Andrea Kronfeld
  6. Felipe Aedo Jury
  7. Pierre-Hugues Prouvot
  8. Consuelo Fois
  9. Franziska Albers
  10. Timo van Alst
  11. Cornelius Faber
  12. Albrecht Stroh
(2017)
Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves
eLife 6:e27602.
https://doi.org/10.7554/eLife.27602

Share this article

https://doi.org/10.7554/eLife.27602

Further reading

    1. Neuroscience
    Alex TL Leong, Ed X Wu
    Insight

    Simultaneous measurements of neuronal activity and fMRI signals in the rat brain have shed new light on the origins of resting-state fMRI connectivity networks.

    1. Neuroscience
    Sandra P Cárdenas-García, Sundas Ijaz, Alberto E Pereda
    Research Article

    Most nervous systems combine both transmitter-mediated and direct cell-cell communication, known as 'chemical' and 'electrical' synapses, respectively. Chemical synapses can be identified by their multiple structural components. Electrical synapses are, on the other hand, generally defined by the presence of a 'gap junction' (a cluster of intercellular channels) between two neuronal processes. However, while gap junctions provide the communicating mechanism, it is unknown whether electrical transmission requires the contribution of additional cellular structures. We investigated this question at identifiable single synaptic contacts on the zebrafish Mauthner cells, at which gap junctions coexist with specializations for neurotransmitter release and where the contact unequivocally defines the anatomical limits of a synapse. Expansion microscopy of these single contacts revealed a detailed map of the incidence and spatial distribution of proteins pertaining to various synaptic structures. Multiple gap junctions of variable size were identified by the presence of their molecular components. Remarkably, most of the synaptic contact's surface was occupied by interleaving gap junctions and components of adherens junctions, suggesting a close functional association between these two structures. In contrast, glutamate receptors were confined to small peripheral portions of the contact, indicating that most of the synaptic area functions as an electrical synapse. Thus, our results revealed the overarching organization of an electrical synapse that operates with not one, but multiple gap junctions, in close association with structural and signaling molecules known to be components of adherens junctions. The relationship between these intercellular structures will aid in establishing the boundaries of electrical synapses found throughout animal connectomes and provide insight into the structural organization and functional diversity of electrical synapses.