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

  • 2,686
    views
  • 401
    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
    Vincent Huson, Wade G Regehr
    Research Article

    Unipolar brush cells (UBCs) are excitatory interneurons in the cerebellar cortex that receive mossy fiber (MF) inputs and excite granule cells. The UBC population responds to brief burst activation of MFs with a continuum of temporal transformations, but it is not known how UBCs transform the diverse range of MF input patterns that occur in vivo. Here, we use cell-attached recordings from UBCs in acute cerebellar slices to examine responses to MF firing patterns that are based on in vivo recordings. We find that MFs evoke a continuum of responses in the UBC population, mediated by three different types of glutamate receptors that each convey a specialized component. AMPARs transmit timing information for single stimuli at up to 5 spikes/s, and for very brief bursts. A combination of mGluR2/3s (inhibitory) and mGluR1s (excitatory) mediates a continuum of delayed, and broadened responses to longer bursts, and to sustained high frequency activation. Variability in the mGluR2/3 component controls the time course of the onset of firing, and variability in the mGluR1 component controls the duration of prolonged firing. We conclude that the combination of glutamate receptor types allows each UBC to simultaneously convey different aspects of MF firing. These findings establish that UBCs are highly flexible circuit elements that provide diverse temporal transformations that are well suited to contribute to specialized processing in different regions of the cerebellar cortex.

    1. Neuroscience
    Eleni Hackwell, Sharon R Ladyman ... David R Grattan
    Research Article

    The specific role that prolactin plays in lactational infertility, as distinct from other suckling or metabolic cues, remains unresolved. Here, deletion of the prolactin receptor (Prlr) from forebrain neurons or arcuate kisspeptin neurons resulted in failure to maintain normal lactation-induced suppression of estrous cycles. Kisspeptin immunoreactivity and pulsatile LH secretion were increased in these mice, even in the presence of ongoing suckling stimulation and lactation. GCaMP fibre photometry of arcuate kisspeptin neurons revealed that the normal episodic activity of these neurons is rapidly suppressed in pregnancy and this was maintained throughout early lactation. Deletion of Prlr from arcuate kisspeptin neurons resulted in early reactivation of episodic activity of kisspeptin neurons prior to a premature return of reproductive cycles in early lactation. These observations show dynamic variation in arcuate kisspeptin neuronal activity associated with the hormonal changes of pregnancy and lactation, and provide direct evidence that prolactin action on arcuate kisspeptin neurons is necessary for suppressing fertility during lactation in mice.