Cholinergic and noncholinergic brainstem neurons expressing Fos after paradoxical (REM) sleep deprivation and recovery

CNRS UMR 5167, Institut Fédératif des Neurosciences de Lyon (IFR 19), Faculté de médecine RTH Laennec, 7, rue Guillaume Paradin, 69372 Lyon Cedex 08, France.
European Journal of Neuroscience (Impact Factor: 3.18). 06/2005; 21(9):2488-504. DOI: 10.1111/j.1460-9568.2005.04060.x
Source: PubMed


It is well accepted that populations of neurons responsible for the onset and maintenance of paradoxical sleep (PS) are restricted to the brainstem. To localize the structures involved and to reexamine the role of mesopontine cholinergic neurons, we compared the distribution of Fos- and choline acetyltransferase-labelled neurons in the brainstem of control rats, rats selectively deprived of PS for approximately 72 h and rats allowed to recover from such deprivation. Only a few cholinergic neurons from the laterodorsal (LDTg) and pedunculopontine tegmental nuclei were Fos-labelled after PS recovery. In contrast, a large number of noncholinergic Fos-labelled cells positively correlated with the percentage of time spent in PS was observed in the LDTg, sublaterodorsal, alpha and ventral gigantocellular reticular nuclei, structures known to contain neurons specifically active during PS. In addition, a large number of Fos-labelled cells were seen after PS rebound in the lateral, ventrolateral and dorsal periaqueductal grey, dorsal and lateral paragigantocellular reticular nuclei and the nucleus raphe obscurus. Interestingly, half of the cells in the latter nucleus were immunoreactive to choline acetyltransferase. In contrast to the well-accepted hypothesis, our results strongly suggest that neurons active during PS, recorded in the mesopontine cholinergic nuclei, are in the great majority noncholinergic. Our findings further demonstrate that many brainstem structures not previously identified as containing neurons active during PS contain cholinergic or noncholinergic neurons active during PS, and these structures may therefore play a key role during this state. Altogether, our results open a new avenue of research to identify the specific role of the populations of neurons revealed, their interrelations and their neurochemical identity.

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Available from: Laure Verret
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    • "In the future, it will be important to employ additional experimental approaches to fully determine the role of these neurons, including tract-tracing, single unit recordings, inactivations and activations by genetic or pharmacological tools. Furthermore, several regions that contain a large number of c-Fos-labeled neurons require additional studies, including the lateral paragigantocellular nucleus, the lateral parabrachial nucleus, the nucleus raphe obscurus and the dorsal PAG (Verret et al., 2005). "
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    ABSTRACT: Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by the loss of muscle atonia during paradoxical (REM) sleep (PS). Conversely, cataplexy, one of the key symptoms of narcolepsy, is a striking sudden episode of muscle weakness triggered by emotions during wakefulness, and comparable to REM sleep atonia. The neuronal dysfunctions responsible for RBD and cataplexy are not known. In the present review, we present the most recent results on the neuronal network responsible for PS. Based on these results, we propose an updated integrated model of the mechanisms responsible for PS and explore different hypotheses explaining RBD and cataplexy. We propose that RBD is due to a specific degeneration of a subpopulation of PS-on glutamatergic neurons specifically responsible of muscle atonia, localized in the caudal pontine sublaterodorsal tegmental nucleus (SLD). Another possibility is the occurrence in RBD patients of a specific lesion of the glycinergic/GABAergic premotor-neurons localized in the medullary ventral gigantocellular reticular nucleus. Conversely, cataplexy in narcoleptics would be due to the activation during waking of the caudal PS-on SLD neurons responsible for muscle atonia. A direct or indirect pathway activated during positive emotion from the central amygdala to the SLD PS-on neurons would induce such activation. In normal conditions, the activation of SLD neurons would be blocked by the simultaneous excitation by the hypocretins of the PS-off GABAergic neurons localized in the ventrolateral periaqueductal gray and the adjacent deep mesencephalic reticular nucleus gating the activation of the PS-on SLD neurons.
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    • "It has indeed been shown that, in rats, the DPGi contains a large population of neurons expressing c-FOS (a marker of neuronal activation) during PS hypersomnia [4]. In addition, electrophysiological recordings in head-restrained rats confirmed the presence in the DPGi of neurons strongly active specifically during PS (PS-on neurons) [5]. "
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    • "In contrast, functional mapping studies using the c-fos method in animals with a compensatory hyper-expression of REMS after sustained periods of REMS deprivation did not report any significant activation of the medial parabrachial nucleus (Verret et al., 2005; Clément et al., 2011). These studies identified clusters of activated neurons in the central subnucleus of the lateral parabrachial complex (Verret et al., 2005; Clément et al., 2011). "
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