The adipocyte hormone leptin sets the emergence of hippocampal inhibition in mice

Marlene Bartos (1) , Camille Dumon , Diabe Diabira (2) , Ilona Chudotvorova (3) , Francesca Bader , Semra Sahin , Jinwei Zhang (4) , Christophe Porcher (5) , Gary Wayman , Igor Medina (2) , Jean-Luc Gaiarsa (3, 2)

1 Institute of Medical Sciences
2 INMED - INSERM U1249 - Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université]
3 Epilepsie et ischémie cérébrale
4 University of Exeter
5 GESIND - Groupe d'Etude du Stress et des Interactions Neuro-Digestives

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.

Mots clés: GABAergic; KCC2; Leptine

Domaines: Neurosciences [q-bio.NC]

Marlene Bartos, Camille Dumon, Diabe Diabira, Ilona Chudotvorova, Francesca Bader, et al.. The adipocyte hormone leptin sets the emergence of hippocampal inhibition in mice. eLife, 2018, 7. ⟨hal-01963638⟩