Localization of the Brainstem GABAergic Neurons Controlling Paradoxical (REM) Sleep

Emilie Sapin, Damien Lapray, Anne Bérod, Romain Goutagny, Lucienne Léger, Pascal Ravassard, Olivier Clément, Lucie Hanriot, Patrice Fort, Pierre-Hervé Luppi
PLoS ONE. 2009-01-26; 4(1): e4272
DOI: 10.1371/journal.pone.0004272

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1. PLoS One. 2009;4(1):e4272. doi: 10.1371/journal.pone.0004272. Epub 2009 Jan 26.

Localization of the brainstem GABAergic neurons controlling paradoxical (REM)
sleep.

Sapin E(1), Lapray D, Bérod A, Goutagny R, Léger L, Ravassard P, Clément O,
Hanriot L, Fort P, Luppi PH.

Author information:
(1)CNRS, UMR5167, Physiopathologie des réseaux neuronaux du cycle veille-sommeil,
Lyon, France.

Paradoxical sleep (PS) is a state characterized by cortical activation, rapid eye
movements and muscle atonia. Fifty years after its discovery, the neuronal
network responsible for the genesis of PS has been only partially identified. We
recently proposed that GABAergic neurons would have a pivotal role in that
network. To localize these GABAergic neurons, we combined immunohistochemical
detection of Fos with non-radioactive in situ hybridization of GAD67 mRNA (GABA
synthesis enzyme) in control rats, rats deprived of PS for 72 h and rats allowed
to recover after such deprivation. Here we show that GABAergic neurons gating PS
(PS-off neurons) are principally located in the ventrolateral periaqueductal gray
(vlPAG) and the dorsal part of the deep mesencephalic reticular nucleus
immediately ventral to it (dDpMe). Furthermore, iontophoretic application of
muscimol for 20 min in this area in head-restrained rats induced a strong and
significant increase in PS quantities compared to saline. In addition, we found a
large number of GABAergic PS-on neurons in the vlPAG/dDPMe region and the
medullary reticular nuclei known to generate muscle atonia during PS. Finally, we
showed that PS-on neurons triggering PS localized in the SLD are not GABAergic.
Altogether, our results indicate that multiple populations of PS-on GABAergic
neurons are distributed in the brainstem while only one population of PS-off
GABAergic neurons localized in the vlPAG/dDpMe region exist. From these results,
we propose a revised model for PS control in which GABAergic PS-on and PS-off
neurons localized in the vlPAG/dDPMe region play leading roles.

DOI: 10.1371/journal.pone.0004272
PMCID: PMC2629845
PMID: 19169414 [Indexed for MEDLINE]

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