Differential origin of the activation of dorsal and ventral dentate gyrus granule cells during paradoxical (REM) sleep in the rat

Abstract

We recently demonstrated that granule cells located in the dorsal dentate gyrus (dDG) are activated by neurons located in the lateral supramammillary nucleus (SumL) during paradoxical sleep (PS) hypersomnia. To determine whether these neurons are glutamatergic and/or GABAergic, we combined FOS immunostaining with in situ hybridization of vesicular glutamate transporter 2 (vGLUT2, a marker of glutamatergic neurons) or that of the vesicular GABA transporter (vGAT, a marker of GABAergic neurons) mRNA in rats displaying PS hypersomnia (PSR). We found that 84 and 76 % of the FOS+ SumL neurons in PSR rats expressed vGLUT2 and vGAT mRNA, respectively. Then, we examined vGLUT2 and FOS immunostaining in the dorsal and ventral DG of PSR rats with a neurochemical lesion of the Sum. In PSR-lesioned animals but not in sham animals, nearly all vGLUT2+ fibers and FOS+ neurons disappeared in the dDG, but not in the ventral DG (vDG). To identify the pathway (s) responsible (s) for the activation of the vDG during PS hypersomnia, we combined Fluorogold (FG) injection in the vDG of PSR rats with FOS staining. We found a large number of neurons FOS-FG+, specifically in the medial entorhinal cortex (ENTm). Altogether, our results suggest that SumL neurons with a unique dual glutamatergic and GABAergic phenotype are responsible for the activation of the dDG during PS hypersomnia, while vDG granule neurons are activated by ENTm cortical neurons. These results suggest differential mechanisms and functions for the activation of the dDG and the vDG granule cells during PS.

Granule cells in the infrapyramidal blade of the dentate gyrus are activated during paradoxical (REM) sleep hypersomnia but not during wakefulness: a study using TRAP mice

“…We finally showed that the lateral supramammillary nucleus (SuML) was the only subcortical structures containing neurons activated during PSR and projecting to the DG. Further, lesion of the SuML induced a disappearance of cFos staining in the dorsal but not the ventral DG 4,5 .…”

Input–output organization of the mouse claustrum

“…The claustrum (CLA) shares widespread connections with the cortex in a variety of mammalian species (Atlan, Terem, Peretz‐Rivlin, Groysman, & Citri, ;Dinopoulos et al, ;LeVay & Sherk, ; Olson & Graybiel, ; Reser et al, ; Sadowski, Morys, Jakubowska‐sadowska, & Narkiewicz, ; Smith & Alloway, ; Tanné‐Gariepy, Boussaoud, & Rouiller, ; Torgerson, Irimia, Goh, & Van Horn, ; Wang et al, ; White et al, ; Zingg et al, ), and has been postulated to play an important role in processes ranging from attention (Goll, Atlan, & Citri, ; White et al, ) and salience detection (Kim, Matney, Roth, & Brown, ; Remedios, Logothetis, & Kayser, , ) to the coordination of rapid eye movement (REM) sleep (Billwiller, Renouard, Clement, Fort, & Luppi, ; Renouard et al, ; for review see Brown et al, ; Crick & Koch, ; Mathur, ). Progress in determining its precise function and anatomical organization, however, has been hindered by the difficulty in targeting CLA neurons for experimental manipulation due to its small, irregular shape.…”

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

“…Indeed, it has been shown that the SuM controls hippocampal theta rhythm (Kocsis and Vertes 1994 ; Vertes and Kocsis 1997 ; Kocsis and Kaminski 2006 ) and is involved in emotional learning and memory (Pasquier and Reinoso-Suarez 1976 ; Richmond et al 1999 ; Pan and McNaughton 2002 ; Santín et al 2003 ; Pan and McNaughton 2004 ; Shahidi et al 2004 ). By combining retrograde tracing, neurotoxic lesion and FOS immunostaining, it was recently shown that SuML GABA/glutamate neurons are responsible for the activation of dDG granule cells during paradoxical sleep (PS) (Renouard et al 2015 ; Billwiller et al 2017 ). Such activation may play a key role in the previously reported beneficial effect of PS on learning and memory (Maquet et al 2000 ).…”