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.
Ethics
Animal experimentation: All animal procedures were carried out in accordance with the European Union Directive of 22 September (2010/63/EU).
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.
Metrics
-
- 1,796
- views
-
- 254
- downloads
-
- 22
- 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)
The adipocyte hormone leptin sets the emergence of hippocampal inhibition in mice
eLife 7:e36726.
https://doi.org/10.7554/eLife.36726
Further reading
-
- Neuroscience
Research on brain plasticity, particularly in the context of deafness, consistently emphasizes the reorganization of the auditory cortex. But to what extent do all individuals with deafness show the same level of reorganization? To address this question, we examined the individual differences in functional connectivity (FC) from the deprived auditory cortex. Our findings demonstrate remarkable differentiation between individuals deriving from the absence of shared auditory experiences, resulting in heightened FC variability among deaf individuals, compared to more consistent FC in the hearing group. Notably, connectivity to language regions becomes more diverse across individuals with deafness. This does not stem from delayed language acquisition; it is found in deaf native signers, who are exposed to natural language since birth. However, comparing FC diversity between deaf native signers and deaf delayed signers, who were deprived of language in early development, we show that language experience also impacts individual differences, although to a more moderate extent. Overall, our research points out the intricate interplay between brain plasticity and individual differences, shedding light on the diverse ways reorganization manifests among individuals. It joins findings of increased connectivity diversity in blindness and highlights the importance of considering individual differences in personalized rehabilitation for sensory loss.
-
- Computational and Systems Biology
- Neuroscience
Fiber photometry has become a popular technique to measure neural activity in vivo, but common analysis strategies can reduce the detection of effects because they condense within-trial signals into summary measures, and discard trial-level information by averaging across-trials. We propose a novel photometry statistical framework based on functional linear mixed modeling, which enables hypothesis testing of variable effects at every trial time-point, and uses trial-level signals without averaging. This makes it possible to compare the timing and magnitude of signals across conditions while accounting for between-animal differences. Our framework produces a series of plots that illustrate covariate effect estimates and statistical significance at each trial time-point. By exploiting signal autocorrelation, our methodology yields joint 95% confidence intervals that account for inspecting effects across the entire trial and improve the detection of event-related signal changes over common multiple comparisons correction strategies. We reanalyze data from a recent study proposing a theory for the role of mesolimbic dopamine in reward learning, and show the capability of our framework to reveal significant effects obscured by standard analysis approaches. For example, our method identifies two dopamine components with distinct temporal dynamics in response to reward delivery. In simulation experiments, our methodology yields improved statistical power over common analysis approaches. Finally, we provide an open-source package and analysis guide for applying our framework.
