Elsevier

Neuroscience

Volume 145, Issue 3, 30 March 2007, Pages 1157-1167
Neuroscience

Systems neuroscience
GABAergic processes in the mesencephalic tegmentum modulate the occurrence of active (rapid eye movement) sleep in guinea pigs

https://doi.org/10.1016/j.neuroscience.2006.12.051Get rights and content

Abstract

The ventrolateral subdivision of the periaqueductal gray (vlPAG) and the adjacent dorsal mesencephalic reticular formation (dMRF) are involved in the modulation of active (rapid eye movement) sleep (AS). In order to determine the effects on AS of the suppression of neuronal activity in these regions, muscimol, a GABA receptor A (GABAA) receptor agonist, and bicuculline, a GABAA receptor antagonist, were microinjected bilaterally in guinea pigs and the states of sleep and wakefulness were examined. The main effect of muscimol was an increase in AS; this increase occurred in conjunction with a reduction in the time spent in wakefulness. The powerful effect of muscimol was striking especially when considering the small amount of naturally-occurring AS that is present in this species. Additional observable effects that were induced by muscimol were: 1) long lasting episodes of hypotonia/atonia during wakefulness and quiet sleep that included a lack of extensor tone in the hind limbs, and 2) frequently occurring cortical spindles, similar to those observed during naturally-occurring quiet sleep (sleep spindles), that were present during wakefulness. Conversely, bilateral microinjections of bicuculline induced a prolonged state of wakefulness and blocked the effect of subsequent injections of muscimol. These data suggest that endogenous GABA acts on GABAA receptors within the vlPAG and dMRF to promote AS in the guinea pig.

Section snippets

Experimental procedures

Adult male guinea pigs (Cavia porcellus) weighing between 450 and 550 g were used in the present study. All experimental procedures were approved by the Commission for Animal Experimentation of the Universidad de la República of Uruguay and were in accordance with the Guide for the Care and Use of Laboratory Animals (7th edition, National Academy Press, Washington, DC, 1996). All efforts were made to minimize the number of animals used in this study, and adequate measures were taken to minimize

Control experiments

Quiet W was the predominant state of the animals after they had been adapted to the recording conditions; this state was interrupted occasionally by brief episodes of sleep. Examples of typical polygraphic recordings obtained under control conditions are shown in Fig. 1A. This figure illustrates the spontaneous presence of naturally-occurring states of W, QS and AS; it should be noted, because this is a characteristic of sleep in these animals that at the beginning of AS there is an incomplete

Discussion

In the present study we demonstrate that the inhibition, by GABAA agonists, in the vlPAG and the adjacent dMRF of the guinea pig, produces AS hypersomnia. This effect is blocked by the GABAA antagonist bicuculline. In addition, collateral effects such as hypotonia/atonia and cortical waking-spindles were present during some of these experiments.

The present study was performed in guinea pigs, as a part of a global research program designed to explore the mechanisms of W and sleep in guinea pigs (

Conclusion

The present report represents a foundation for anatomical and physiological studies designed to elucidate the mechanisms and neuronal systems involved in the physiological modulation of AS by mesencephalic sites, specifically the vlPAG and the dMRF. We suggest that these sites contain wake-promoting neurons that are likely inhibited by GABAergic systems; when these GABAergic systems are activated, AS occurs.

Acknowledgments

We are grateful to J. K. Engelhardt for his critical review of this manuscript. This work was supported by the following grants from the U.S. Public Health Service: NS23426, NS09999, and MH43362.

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