PT  - JOURNAL ARTICLE
AU  - Francesca Billwiller
AU  - Laura Castillo
AU  - Heba Elseedy
AU  - Anton Ivanovich Ivanov
AU  - Jennyfer Scapula
AU  - Antoine Ghestem
AU  - Julien Carponcy
AU  - Paul Antoine Libourel
AU  - Hélène Bras
AU  - Nabila ElSayed Abdelmeguid
AU  - Esther Krook-Magnuson
AU  - Ivan Soltesz
AU  - Christophe Bernard
AU  - Pierre-Hervé Luppi
AU  - Monique Esclapez
TI  - GABA-Glutamate supramammillary neurons control theta and gamma oscillations in the dentate gyrus during paradoxical (REM) sleep
AID  - 10.1101/584862
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 584862
4099  - http://biorxiv.org/content/early/2019/05/14/584862.short
4100  - http://biorxiv.org/content/early/2019/05/14/584862.full
AB  - Several studies suggest that neurons from the lateral region of the SuM (SuML) innervating the dorsal dentate gyrus (DG) display a dual GABAergic and glutamatergic transmission and are specifically activated during paradoxical (REM) sleep (PS). The objective of the present study is to fully characterize the anatomical, neurochemical and electrophysiological properties of the SuML-DG projection neurons and to determine how they control DG oscillations and neuronal activation during PS and other vigilance states. For this purpose, we combine structural connectivity techniques using neurotropic viral vectors (rabies virus, AAV), neurochemical anatomy (immunohistochemistry, in situ hybridization) and imaging (light, electron and confocal microscopy) with in vitro (patch clamp) and in vivo (LFP, EEG) optogenetic and electrophysiological recordings performed in transgenic VGLUT2-cre male mice. At the cellular level, we show that the SuML-DG neurons co-release GABA and glutamate on dentate granule cells and increase the activity of a subset of DG granule cells. At the network level, we show that activation of the SuML-DG pathway increases theta power and frequency during PS as well as gamma power during PS and waking in the DG. At the behavioral level, we show that the activation of this pathway does not change animal behavior during PS, induces awakening during slow wave sleep and increases motor activity during waking. These results suggest that the SuML-DG pathway is capable of supporting the increase of theta and gamma power in the DG observed during PS and plays an important modulatory role of DG network activity during this state.Significant statement An increase of theta and gamma power in the dentate gyrus (DG) is an hallmark of paradoxical (REM) sleep (PS) and is suggested to promote learning and memory consolidation by synchronizing hippocampal networks and increasing its outputs to cortical targets. However the neuronal networks involved in such control of DG activity during PS are poorly understood. The present study identifies a population of GABA/Glutamate neurons in the lateral supramammllary nucleus (SuML) innervating the DG that could support such control during PS. Indeed, we show that activation of these SuML-DG projections increase theta power and frequency as well as gamma power in the DG specifically during PS and modulate activity of a subset of DG granule cells.