Aberrant sorting of hippocampal complex pyramidal cells in Type I Lissencephaly alters topological innervation
- 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.
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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.
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Author details
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.
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.
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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Aberrant sorting of hippocampal complex pyramidal cells in Type I Lissencephaly alters topological innervation
eLife 9:e55173.
https://doi.org/10.7554/eLife.55173
