The adipocyte hormone leptin sets the emergence of hippocampal inhibition in mice
- Aix-Marseille University UMR 1249, INSERM (Institut National de la Santé et de la Recherche Médicale), France
- Washington State University, United States
- University of Exeter Medical School, United Kingdom
Abstract
Brain computations rely on a proper balance between excitation and inhibition which progressively emerges during postnatal development in rodent. g-aminobutyric acid (GABA) neurotransmission supports inhibition in the adult brain but excites immature rodent neurons. Alterations in the timing of the GABA switch contribute to neurological disorders, so unveiling the involved regulators may be a promising strategy for treatment. Here we show that the adipocyte hormone leptin sets the tempo for the emergence of GABAergic inhibition in the newborn rodent hippocampus. In the absence of leptin signaling, hippocampal neurons show an advanced emergence of GABAergic inhibition. Conversely, maternal obesity associated with hyperleptinemia delays the excitatory to inhibitory switch of GABA action in offspring. This study uncovers a developmental function of leptin that may be linked to the pathogenesis of neurological disorders and helps understanding how maternal environment can adversely impact offspring brain development.
Data availability
All data generated or analyszed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1 to 4 and Supplementary Figures 1 and 2.
Article and author information
Author details
Funding
National Institutes of Health (Grant MH086032)
- Gary Wayman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Marlene Bartos, University of Freiburg, Germany
Ethics
Animal experimentation: All animal procedures were carried out in accordance with the European Union Directive of 22 September (2010/63/EU).
Version history
- Received: March 16, 2018
- Accepted: August 9, 2018
- Accepted Manuscript published: August 14, 2018 (version 1)
- Version of Record published: August 28, 2018 (version 2)
- Version of Record updated: December 4, 2018 (version 3)
Copyright
© 2018, Dumon 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.
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The adipocyte hormone leptin sets the emergence of hippocampal inhibition in mice
eLife 7:e36726.
https://doi.org/10.7554/eLife.36726
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