Aberrant sorting of hippocampal complex pyramidal cells in Type I Lissencephaly alters topological innervation

  1. James A D'Amour
  2. Tyler Ekins
  3. Stuti Ganatra
  4. Xiaoqing Yuan
  5. Chris J McBain  Is a corresponding author
  1. Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States

Abstract

Layering has been a long-appreciated feature of higher order mammalian brain structures but the extent to which it plays an instructive role in synaptic specification remains unknown. Here we examine the formation of synaptic circuitry under cellular heterotopia in hippocampal CA1, using a mouse model of the human neurodevelopmental disorder Type I Lissencephaly. We identify calbindin-expressing principal cells which are mispositioned under cellular heterotopia. Ectopic calbindin-expressing principal cells develop relatively normal morphological features and stunted intrinsic physiological features. Regarding network development, a connectivity preference for cholecystokinin-expressing interneurons to target calbindin-expressing principal cells is diminished. Moreover, in vitro gamma oscillatory activity is less synchronous across heterotopic bands and mutants are less responsive to pharmacological inhibition of cholecystokinin-containing interneurons. This study will aid not only in our understanding of how cellular networks form but highlight vulnerable cellular circuit motifs that might be generalized across disease states.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures.

Article and author information

Author details

  1. James A D'Amour

    Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Tyler Ekins

    Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Stuti Ganatra

    Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Xiaoqing Yuan

    Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Chris J McBain

    Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes 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

National Institute of General Medical Sciences (Fi2 GM123992)

  • James A D'Amour

Eunice Kennedy Shriver National Institute of Child Health and Human Development

  • Chris J McBain

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

Reviewing Editor

  1. Inna Slutsky, Tel Aviv University, Israel

Ethics

Animal experimentation: All experiments were conducted in accordance with animal protocols approved by the National Institutes of Health Animal Care and Use Committee (protocol 11-045). All practices aligned with the recommendations of the American Veterinary Medical Association. Care was taken to minimize any suffering.

Version history

  1. Received: January 15, 2020
  2. Accepted: June 19, 2020
  3. Accepted Manuscript published: June 19, 2020 (version 1)
  4. Version of Record published: July 7, 2020 (version 2)

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.

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  1. James A D'Amour
  2. Tyler Ekins
  3. Stuti Ganatra
  4. Xiaoqing Yuan
  5. Chris J McBain
(2020)
Aberrant sorting of hippocampal complex pyramidal cells in Type I Lissencephaly alters topological innervation
eLife 9:e55173.
https://doi.org/10.7554/eLife.55173

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https://doi.org/10.7554/eLife.55173

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