GABA–glutamate supramammillary neurons control theta and gamma oscillations in the dentate gyrus during paradoxical (REM) sleep

Francesca Billwiller, Laura Castillo, Heba Elseedy, Anton Ivanovich Ivanov, Jennyfer Scapula, Antoine Ghestem, Julien Carponcy, Paul Antoine Libourel, Hélène Bras, Nabila El Sayed Abdelmeguid, Esther Krook-Magnuson, Ivan Soltesz, Christophe Bernard, Pierre Hervé Luppi, Monique Esclapez

Research output: Contribution to journalArticlepeer-review

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)2643-2668
Number of pages26
JournalBrain Structure and Function
Volume225
Issue number9
DOIs
StatePublished - Dec 2020

Bibliographical note

Funding Information:
This work was supported by INSERM and Aix-Marseille University (M. E., H. E., C. B., L. C., AI. I., A. G., J. S.); Partenariats Hubert Curien (PHC) IMHOTEP (M. E., H. E., NE. A.); Agence Universitaire Francophone (H. E.); Ministry of Scientific Research, Egypt (H. E., NE. A.); CNRS, Fondation pour la recherche médicale (FRM), Société Française de Recherche et Médecine du Sommeil (SFRMS), University Claude Bernard of Lyon (F. B., P-H. L., P-A. L., S. A.) and NS104590 (I. S., E. K-M.). Acknowledgements

Funding Information:
We thank the animal facility (CEFOS, AMU, Marseille), the imaging facility (INPHIM, AMU, Marseille) and the electron microscope facility (IBDM, Marseille).

Publisher Copyright:
© 2020, The Author(s).

Keywords

  • GAD
  • Hippocampus
  • Hypothalamus
  • SuM
  • VGAT
  • VGLUT2

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