Activity-dependent tuning of intrinsic excitability in mouse and human neurogliaform cells

  1. Ramesh Chittajallu  Is a corresponding author
  2. Kurt Auville
  3. Vivek Mahadevan
  4. Mandy Lai
  5. Steven Hunt
  6. Daniela Calvigioni
  7. Kenneth A Pelkey
  8. Kareem A Zaghloul
  9. Chris J McBain  Is a corresponding author
  1. Eunice Kennedy Shriver National Insititute of Child Helath and Human Development, National Insitutes of Health, United States
  2. National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States

Abstract

The ability to modulate the efficacy of synaptic communication between neurons constitutes an essential property critical for normal brain function. Animal models have proved invaluable in revealing a wealth of diverse cellular mechanisms underlying varied plasticity modes. However, to what extent these processes are mirrored in humans is largely uncharted thus questioning their relevance in human circuit function. In this study, we focus on neurogliaform cells, that possess specialized physiological features enabling them to impart a widespread inhibitory influence on neural activity. We demonstrate that this prominent neuronal subtype, embedded in both mouse and human neural circuits, undergo remarkably similar activity-dependent modulation manifesting as epochs of enhanced intrinsic excitability. In principle, these evolutionary conserved plasticity routes likely tune the extent of neurogliaform cell mediated inhibition thus constituting canonical circuit mechanisms underlying human cognitive processing and behavior.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting source data files.

The following previously published data sets were used
    1. Allen Brain Institute - Hodge et al. doi:10.1038/s41586-019-1506-7
    (2019) Cell Diversity in the Mouse Cortex and Hippocampus & Cell Diversity in the Human cortex
    https://transcriptomic-viewer-downloads.s3-us-west-2.amazonaws.com/mouse/transcriptome.zip; https://transcriptomic-viewer-downloads.s3-us-west-2.amazonaws.com/human/transcriptome.zip.

Article and author information

Author details

  1. Ramesh Chittajallu

    Section on Cellular and Synaptic Physiology, Eunice Kennedy Shriver National Insititute of Child Helath and Human Development, National Insitutes of Health, Bethesda, United States
    For correspondence
    ramesh.chittajallu@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9794-0052
  2. Kurt Auville

    Section on Cellular and Synaptic Physiology, Eunice Kennedy Shriver National Insititute of Child Helath and Human Development, National Insitutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Vivek Mahadevan

    Laboratory of Cellular and Synaptic Physiology, Eunice Kennedy Shriver National Insititute of Child Helath and Human Development, National Insitutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0805-827X
  4. Mandy Lai

    Section on Cellular and Synaptic Physiology, Eunice Kennedy Shriver National Insititute of Child Helath and Human Development, National Insitutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Steven Hunt

    Laboratory of Cellular and Synaptic Physiology, Eunice Kennedy Shriver National Insititute of Child Helath and Human Development, National Insitutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Daniela Calvigioni

    Laboratory of Cellular and Synaptic Physiology, Eunice Kennedy Shriver National Insititute of Child Helath and Human Development, National Insitutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Kenneth A Pelkey

    Section on Cellular and Synaptic Physiology, Eunice Kennedy Shriver National Insititute of Child Helath and Human Development, National Insitutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9731-1336
  8. Kareem A Zaghloul

    Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8575-3578
  9. Chris J McBain

    Section on Cellular and Synaptic Physiology, Eunice Kennedy Shriver National Insititute of Child Helath and Human Development, National Insitutes of Health, Bethesda, United States
    For correspondence
    mcbainc@mail.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5909-0157

Funding

NINDS Intramural Research Program (Z01NS003144)

  • Kareem A Zaghloul

NICHD Intramural Research Program (ZIAHD001205)

  • Chris J McBain

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 mice were handled in accordance with animal protocols approved by the National Institutes of Health (ASP# 17-045).

Human subjects: The NINDS Institutional Review Board (IRB) approved the research protocol (ClinicalTrials.gov Identifier NCT01273129), and informed consent for the experimental use of resected tissue was obtained from each participant and their guardians.

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

  • 2,697
    views
  • 402
    downloads
  • 31
    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. Ramesh Chittajallu
  2. Kurt Auville
  3. Vivek Mahadevan
  4. Mandy Lai
  5. Steven Hunt
  6. Daniela Calvigioni
  7. Kenneth A Pelkey
  8. Kareem A Zaghloul
  9. Chris J McBain
(2020)
Activity-dependent tuning of intrinsic excitability in mouse and human neurogliaform cells
eLife 9:e57571.
https://doi.org/10.7554/eLife.57571

Share this article

https://doi.org/10.7554/eLife.57571

Further reading

    1. Neuroscience
    Hans Martin Kjer, Mariam Andersson ... Tim B Dyrby
    Research Article

    We used diffusion MRI and x-ray synchrotron imaging on monkey and mice brains to examine the organisation of fibre pathways in white matter across anatomical scales. We compared the structure in the corpus callosum and crossing fibre regions and investigated the differences in cuprizone-induced demyelination in mouse brains versus healthy controls. Our findings revealed common principles of fibre organisation that apply despite the varying patterns observed across species; small axonal fasciculi and major bundles formed laminar structures with varying angles, according to the characteristics of major pathways. Fasciculi exhibited non-straight paths around obstacles like blood vessels, comparable across the samples of varying fibre complexity and demyelination. Quantifications of fibre orientation distributions were consistent across anatomical length scales and modalities, whereas tissue anisotropy had a more complex relationship, both dependent on the field-of-view. Our study emphasises the need to balance field-of-view and voxel size when characterising white matter features across length scales.

    1. Neuroscience
    Sergio Plaza-Alonso, Nicolas Cano-Astorga ... Lidia Alonso-Nanclares
    Research Article Updated

    The entorhinal cortex (EC) plays a pivotal role in memory function and spatial navigation, connecting the hippocampus with the neocortex. The EC integrates a wide range of cortical and subcortical inputs, but its synaptic organization in the human brain is largely unknown. We used volume electron microscopy to perform a 3D analysis of the microanatomical features of synapses in all layers of the medial EC (MEC) from the human brain. Using this technology, 12,974 synapses were fully 3D reconstructed at the ultrastructural level. The MEC presented a distinct set of synaptic features, differentiating this region from other human cortical areas. Furthermore, ultrastructural synaptic characteristics within the MEC was predominantly similar, although layers I and VI exhibited several synaptic characteristics that were distinct from other layers. The present study constitutes an extensive description of the synaptic characteristics of the neuropil of all layers of the EC, a crucial step to better understand the connectivity of this cortical region, in both health and disease.