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

Sapin E, Lapray D, Bérod A, Goutagny R, Léger L, Ravassard P, Clément O, Hanriot L, Fort P, Luppi PH - PLoS ONE (2009)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: CNRS, UMR5167, Physiopathologie des réseaux neuronaux du cycle veille-sommeil, Lyon, France.

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.

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Paradoxical sleep characteristics after muscimol injection in the vlPAG/dDpMe region.A: EEG spectrogram analysis of the 3000 s following one Mus ejection in the vlPAG/dDpMe region. Rectified EMG amplitude, EEG trace and spectrogram analysis are presented for 200 s corresponding to one PS episode induced by the Mus ejection. B: PS episodes induced by Mus ejections share the same properties as the control one, an active EOG, a flat EMG and a dominant theta band frequency activity. C: Average power spectrum analysis for Mus and NaCl ejections in the vlPAG/dDpMe region.
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pone-0004272-g005: Paradoxical sleep characteristics after muscimol injection in the vlPAG/dDpMe region.A: EEG spectrogram analysis of the 3000 s following one Mus ejection in the vlPAG/dDpMe region. Rectified EMG amplitude, EEG trace and spectrogram analysis are presented for 200 s corresponding to one PS episode induced by the Mus ejection. B: PS episodes induced by Mus ejections share the same properties as the control one, an active EOG, a flat EMG and a dominant theta band frequency activity. C: Average power spectrum analysis for Mus and NaCl ejections in the vlPAG/dDpMe region.

Mentions: In contrast, following injections of Mus into the vlPAG/dDpMe region (n = 5) (Figures 4 and S5), a dramatic increase in PS quantities (31.9±2.4% of total time) was observed compared to saline injections (9.3±2.9% of total time). PS quantities were increased by 342% compared to NaCl (p = 0.0003) concomitant to a non significant decrease of SWS and W. The dramatic increase of PS was due to an increase in the number of PS episodes (1.3±0.3 for NaCl versus 3.5±0.2 episodes for Mus, an increase of 260%, p = 0.0007) and not of their duration (1.8±0.15 min versus 1.3±0.4 min). The increase of PS started with a mean latency of 7.1±1.3 min and ended 1 hour after the beginning of the Mus injection (Figure 4B). Importantly, 17.3% of the episodes of PS occurring after Mus injections appeared directly after W without a transition by SWS like after saline injections. The episodes of PS occurring after Mus and saline injections were similarly characterized by a cortical EEG desynchronization combined with a muscle atonia and rapid eyes and vibrissae movements (Figure 5A, B and video S1). They also showed the same spectral composition of the EEG (Figure 5C).


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

Sapin E, Lapray D, Bérod A, Goutagny R, Léger L, Ravassard P, Clément O, Hanriot L, Fort P, Luppi PH - PLoS ONE (2009)

Paradoxical sleep characteristics after muscimol injection in the vlPAG/dDpMe region.A: EEG spectrogram analysis of the 3000 s following one Mus ejection in the vlPAG/dDpMe region. Rectified EMG amplitude, EEG trace and spectrogram analysis are presented for 200 s corresponding to one PS episode induced by the Mus ejection. B: PS episodes induced by Mus ejections share the same properties as the control one, an active EOG, a flat EMG and a dominant theta band frequency activity. C: Average power spectrum analysis for Mus and NaCl ejections in the vlPAG/dDpMe region.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2629845&req=5

pone-0004272-g005: Paradoxical sleep characteristics after muscimol injection in the vlPAG/dDpMe region.A: EEG spectrogram analysis of the 3000 s following one Mus ejection in the vlPAG/dDpMe region. Rectified EMG amplitude, EEG trace and spectrogram analysis are presented for 200 s corresponding to one PS episode induced by the Mus ejection. B: PS episodes induced by Mus ejections share the same properties as the control one, an active EOG, a flat EMG and a dominant theta band frequency activity. C: Average power spectrum analysis for Mus and NaCl ejections in the vlPAG/dDpMe region.
Mentions: In contrast, following injections of Mus into the vlPAG/dDpMe region (n = 5) (Figures 4 and S5), a dramatic increase in PS quantities (31.9±2.4% of total time) was observed compared to saline injections (9.3±2.9% of total time). PS quantities were increased by 342% compared to NaCl (p = 0.0003) concomitant to a non significant decrease of SWS and W. The dramatic increase of PS was due to an increase in the number of PS episodes (1.3±0.3 for NaCl versus 3.5±0.2 episodes for Mus, an increase of 260%, p = 0.0007) and not of their duration (1.8±0.15 min versus 1.3±0.4 min). The increase of PS started with a mean latency of 7.1±1.3 min and ended 1 hour after the beginning of the Mus injection (Figure 4B). Importantly, 17.3% of the episodes of PS occurring after Mus injections appeared directly after W without a transition by SWS like after saline injections. The episodes of PS occurring after Mus and saline injections were similarly characterized by a cortical EEG desynchronization combined with a muscle atonia and rapid eyes and vibrissae movements (Figure 5A, B and video S1). They also showed the same spectral composition of the EEG (Figure 5C).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: CNRS, UMR5167, Physiopathologie des réseaux neuronaux du cycle veille-sommeil, Lyon, France.

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.

Show MeSH