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.

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 microgram/0.5 microliter) 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 micrograms), 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 micrograms. 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.