1. Neuroscience
Download icon

Microglial calcium signaling is attuned to neuronal activity in awake mice

Research Article
  • Cited 12
  • Views 3,096
  • Annotations
Cite this article as: eLife 2020;9:e56502 doi: 10.7554/eLife.56502

Abstract

Microglial calcium signaling underlies a number of key physiological processes in situ, but has not been studied in vivo in awake mice. Using multiple GCaMP6 variants targeted to microglia, we assessed how microglial calcium signaling responds to alterations in neuronal activity across a wide physiological range. We find that only a small subset of microglial somata and processes exhibited spontaneous calcium transients in a chronic window preparation. However, hyperactive shifts in neuronal activity (kainate status epilepticus and CaMKIIa Gq DREADD activation) trigger increased microglial process calcium signaling, often concomitant with process extension. Additionally, hypoactive shifts in neuronal activity (isoflurane anesthesia and CaMKIIa Gi DREADD activation) also trigger microglial process calcium signaling. Under hypoactive neuronal conditions, microglia also exhibit process extension and outgrowth with high calcium signaling. Our work reveals that microglia have highly distinct microdomain signaling, and that processes specifically respond to bi-directional shifts in neuronal activity through increased calcium signaling.

Article and author information

Author details

  1. Anthony D Umpierre

    Neurology, Mayo Clinic, Rochester, United States
    For correspondence
    umpierre.anthony@mayo.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1470-8881
  2. Lauren L Bystrom

    Neurology, Mayo Clinic, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yanlu Ying

    Neurology, Mayo Clinic, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yong U Liu

    Neurology, Mayo Clinic, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Gregory Worrell

    Neurology, Mayo Clinic, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Long-Jun Wu

    Neurology, Mayo Clinic, Rochester, United States
    For correspondence
    Wu.LongJun@mayo.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8019-3380

Funding

National Institute of Neurological Disorders and Stroke (NS114040)

  • Anthony D Umpierre

National Institute of Neurological Disorders and Stroke (NS112144)

  • Gregory Worrell
  • Long-Jun Wu

National Institute of Neurological Disorders and Stroke (NS088627)

  • Long-Jun Wu

National Institute of Neurological Disorders and Stroke (NS110825)

  • Long-Jun Wu

National Institute of Neurological Disorders and Stroke (NS110949)

  • Long-Jun Wu

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 experimental procedures were approved by the Mayo Clinic's Institutional Animal Care and Use Committee (IACUC, protocol #2731-17) and were conducted in accordance with the NIH Guide for the Care and Use of Laboratory Animals.

Reviewing Editor

  1. Dwight E Bergles, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: February 29, 2020
  2. Accepted: July 14, 2020
  3. Accepted Manuscript published: July 27, 2020 (version 1)
  4. Version of Record published: August 4, 2020 (version 2)

Copyright

© 2020, Umpierre 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

  • 3,096
    Page views
  • 511
    Downloads
  • 12
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, 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
    Qiang Qiu et al.
    Research Article Updated

    Animals possess an inborn ability to recognize certain odors to avoid predators, seek food, and find mates. Innate odor preference is thought to be genetically hardwired. Here we report that acquisition of innate odor recognition requires spontaneous neural activity and is influenced by sensory experience during early postnatal development. Genetic silencing of mouse olfactory sensory neurons during the critical period has little impact on odor sensitivity, discrimination, and recognition later in life. However, it abolishes innate odor preference and alters the patterns of activation in brain centers. Exposure to innately recognized odors during the critical period abolishes the associated valence in adulthood in an odor-specific manner. The changes are associated with broadened projection of olfactory sensory neurons and expression of axon guidance molecules. Thus, a delicate balance of neural activity is needed during the critical period in establishing innate odor preference and convergent axon input is required to encode innate odor valence.

    1. Computational and Systems Biology
    2. Neuroscience
    Shivesh Chaudhary et al.
    Research Article Updated

    Although identifying cell names in dense image stacks is critical in analyzing functional whole-brain data enabling comparison across experiments, unbiased identification is very difficult, and relies heavily on researchers’ experiences. Here, we present a probabilistic-graphical-model framework, CRF_ID, based on Conditional Random Fields, for unbiased and automated cell identification. CRF_ID focuses on maximizing intrinsic similarity between shapes. Compared to existing methods, CRF_ID achieves higher accuracy on simulated and ground-truth experimental datasets, and better robustness against challenging noise conditions common in experimental data. CRF_ID can further boost accuracy by building atlases from annotated data in highly computationally efficient manner, and by easily adding new features (e.g. from new strains). We demonstrate cell annotation in Caenorhabditis elegans images across strains, animal orientations, and tasks including gene-expression localization, multi-cellular and whole-brain functional imaging experiments. Together, these successes demonstrate that unbiased cell annotation can facilitate biological discovery, and this approach may be valuable to annotation tasks for other systems.