Abstract
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.
Highlights
Paradoxical sleep (PS) or REM sleep is characterized by cortical activation, rapid eye movements and muscle atonia
Combining retrograde tracing with cholera toxin B subunit (CTb) and glutamate decarboxylase (GAD) immunostaining, we proposed that these PS-off GABAergic neurons could be localized in three areas namely the ventrolateral periaqueductal gray and the dorsal part of the deep mesencephalic reticular nucleus, the caudal pontine reticular nucleus (PnC) and/or the sublaterodorsal tegmental nucleus (SLD) itself [2]
Combining CTb and GAD or CTb and Fos immunostaining after PS hypersomnia, we proposed that the PS-on GABAergic neurons at the origin of this inhibition would be localized in the ventrolateral periaqueductal gray (vlPAG) and the dorsal paragigantocellular reticular nucleus (DPGi) [6,7]
Summary
Paradoxical sleep (PS) or REM sleep is characterized by cortical activation, rapid eye movements and muscle atonia. We recently showed in the rat that neurons generating PS are active during PS (PS-on or REM-on neurons) and localized in the sublaterodorsal tegmental nucleus (SLD). We further demonstrated that the activation of these putative glutamatergic neurons is gated by GABAergic neurons active during waking (W) and slow wave sleep (SWS) (PS-off or REM-off neurons) [1]. Lu et al [4] showed that part of the SLD PS-on neurons could be GABAergic combining GAD and Fos staining after PS hypersomnia. They proposed that these GABAergic neurons are responsible for PS genesis by means of reciprocal projections with vlPAG/dDpMe PS-off GABAergic neurons. The existence of these neurons still remained to be demonstrated
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