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: 3.67). 06/2005; 21(9):2488-504. DOI: 10.1111/j.1460-9568.2005.04060.x
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Laure Verret, Jul 02, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The parabrachial complex is classically seen as a major neural knot that transmits viscero- and somatosensory information towards the limbic and thalamic forebrain. In the present review we summarize recent findings that imply an emerging role of the parabrachial complex as an integral part of the ascending reticular arousal system, which promotes wakefulness and cortical activation. The ascending parabrachial projections that target wake-promoting hypothalamic areas and the basal forebrain are largely glutamatergic. Such fast synaptic transmission could be even more significant in promoting wakefulness and its characteristic pattern of cortical activation than the cholinergic or mono-aminergic ascending pathways that have been emphasized extensively in the past. A similar role of the parabrachial complex could also apply for its more established function in control of breathing. Here the parabrachial respiratory neurons may modulate and adapt breathing via the control of respiratory phase transition and upper airway patency, particularly during respiratory and non-respiratory behavior associated with wakefulness.
    Respiratory Physiology & Neurobiology 06/2013; 188(3). DOI:10.1016/j.resp.2013.06.019 · 1.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by the occurrence of intense movements during rapid eye movement (REM) sleep, also named paradoxical sleep. The neuronal dysfunctions at the origin of the loss of atonia in RBD patients are not known. One possibility is that RBD is due to the degeneration of neurons inducing the muscle atonia of REM sleep. Therefore, in our paper we review data on the populations of neurons responsible for the atonia of REM sleep before discussing their potential role in RBD. We first review evidence that motoneurons are tonically hyperpolarized by gamma-aminobutyric acid (GABA) and glycine and phasically excited by glutamate during REM sleep. Then, we review data indicating that the atonia of REM sleep is induced by glycinergic/GABAergic REM-on premotoneurons contained within the raphe magnus and the ventral and alpha gigantocellular reticular nuclei localized in the ventral medullary reticular formation. These neurons are excited during REM sleep by a direct projection from glutamatergic REM-on neurons localized in the pontine sublaterodorsal tegmental nucleus (SLD). From these results, we discuss the possibility that RBD is due to a specific degeneration of descending REM-on glutamatergic neurons localized in the caudal SLD or that of the REM-on GABA/glycinergic premotoneurons localized in the ventral medullary reticular formation. We then propose that movements of RBD are induced by descending projections of cortical motor neurons before discussing possible modes of action of clonazepam and melatonin.
    Sleep Medicine 06/2013; DOI:10.1016/j.sleep.2013.02.004 · 3.10 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Serotonin type 1A (5-HT(1A)) receptor-responsive neurons in the pedunculopontine tegmental nucleus (PPTn) become maximally active immediately before and during rapid eye movement (REM) sleep. A prevailing model of REM sleep generation indicates that activation of such neurons contributes significantly to the generation of REM sleep, and if correct then inactivation of such neurons ought to suppress REM sleep. We test this hypothesis using bilateral microperfusion of the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 10 μm) into the PPTn; this tool has been shown to selectively silence REM sleep-active PPTn neurons while the activity of wake/REM sleep-active PPTn neurons is unaffected. Contrary to the prevailing model, bilateral microperfusion of 8-OH-DPAT into the PPTn (n = 23 rats) significantly increased REM sleep both as a percentage of the total recording time and sleep time, compared with both within-animal vehicle controls and between-animal time-controls. This increased REM sleep resulted from an increased frequency of REM sleep bouts but not their duration, indicating an effect on mechanisms of REM sleep initiation but not maintenance. Furthermore, an increased proportion of the REM sleep bouts stemmed from periods of low REM sleep drive quantified electrographically. Targeted suppression of 5-HT(1A) receptor-responsive PPTn neurons also increased respiratory rate and respiratory-related genioglossus activity, and increased the frequency and amplitude of the sporadic genioglossus activations occurring during REM sleep. These data indicate that 5-HT(1A) receptor-responsive PPTn neurons normally function to restrain REM sleep by elevating the drive threshold for REM sleep induction, and restrain the expression of respiratory rate and motor activities.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 02/2012; 32(5):1622-33. DOI:10.1523/JNEUROSCI.5700-10.2012 · 6.75 Impact Factor