Elsevier

Neuroscience

Volume 74, Issue 2, 19 July 1996, Pages 415-426
Neuroscience

Importance of the ventrolateral region of the periaqueductal gray and adjacent tegmentum in the control of paradoxical sleep as studied by muscimol microinjections in the cat

https://doi.org/10.1016/0306-4522(96)00190-XGet rights and content

Abstract

It has been demonstrated that coagulation in the area of the periaqueductal gray induces a marked increase in paradoxical sleep in the cat [Petitjean F. et al. (1975) Brain Res. 88, 439–453]. This effect was obtained either by the destruction of ascending or descending fibres or by the lesion of a specific group of local neurons. To assess the role of these neurons, muscimol (0.5 μg/0.5 μl) was injected bilaterally in 31 cats in this area of the periaqueductal gray. Polygraphic recordings were performed before and after injections. Following muscimol (GABAA agonist) injection, there was a consistent increase in paradoxical sleep lasting 269 ± 8 min (mean ± S.E.M.), with a latency of 31 ± 2 min. The increase varied from small (20–30%) to medium (30–50%) to large (50–100% of the recording time), depending on the injection site. The intensity of hypersomnia was correlated with the site of the injection. That is, the most profound hypersomnia was obtained when muscimol was injected in the vicinity of a target area which lies in the ventrolateral periaqueductal gray (at the level of the fourth nucleus) and in the reticular formation situated immediately below. Similar effects were also obtained in insomniac cats pretreated with p-chlorophenylalanine and in cats whose brainstem was transected 3 mm rostral to the injection site. Injections of baclofen, a GABAB agonist (0.25–5 μg), did not alter the quantity of paradoxical sleep, whereas injections of bicuculline, a GABAA antagonist, significantly decreased the quantity of paradoxical sleep at the doses of 0.2–2 μg.

It was concluded that inactivation of ventrolateral periaqueductal gray neurons induces a very important increase in paradoxical sleep. The exact mechanisms of this effect remain to be investigated.

Section snippets

Experimental procedures

A total of 31 cats, male and female (2.2–4.7 kg), were employed in this study. Non-pretreated normal cats received muscimol (n = 23), saline (n = 3), bicuculline (n = 6) or baclofen (n = 6) microinjections. In addition, five cats were pretreated with p-chlorophenylalanine (PCPA) before muscimol microinjections, whereas three other cats received muscimol in the target area three to seven days after a total transection of the brainstem at the A4 plane and removal of the cerebrum (see below in Pontine

Physiological and clinical effects

In all cases the cats had to be restrained for 6 min during the bilateral injection of muscimol. We performed a total of 86 injections: 53 were followed by hypersomnia, and when injections were performed either above, below, lateral or medial to the target area (33 cases), we obtained either no effect upon PS or a 2–3 h suppression of PS or a specific increase in SWS2. In some cases, the cat appeared to be looking and searching for unknown objects. This resembles the “hallucinatory behaviour”

Discussion

The present study demonstrates that muscimol microinjections in the ventrolateral portion of the posterior PAG and its immediate vicinity are followed by a very large increase in PS (up to 100% of the recording time during a 5-h period). To the best of our knowledge, this is the only place in the brain in which the injection of a small amount of muscimol is followed by such a dramatic hypersomnia in the cat.26, 43

Conclusions

The bilateral inactivation of the caudal intermediate ventrolateral area of the PAG by microinjections of muscimol is followed by a dramatic increase in PS. This effect is mediated by descending pathways acting upon either executive or permissive mechanisms of PS.

Acknowledgements

We are grateful for the assistance of G. Debilly with statistical data analysis. We also thank M. Schmidt and C. Limoge for correction of the English. Part of this work was presented at the 12th Congress of the European Sleep Research Society held in Florence in May 1994. This study was supported by CNRS URA 1195, DRET (91130) and INSERM U52.

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