Neurotoxic N-methyl-D-aspartate lesion of the ventral midbrain and mesopontine junction alters sleep-wake organization

The dorsal regions of the midbrain and pens have been found to participate in sleep regulation. However, the physiological role of the ventral brainst em in sleep regulation remains unclear. We used N-methyl-D-aspartate-induce d lesions of the Ventral midbrain and pens to address this question. Unlike dorsal mesencephalic reticular formation lesions, which produce somnolence and electroencephalogram synchronization, we found that ventral midbrain l esions produce insomnia and hyperactivity. Marked increases in waking and d ecreases in slow wave sleep stage 1 (S1), stage 2 (S2) and rapid eye moveme nt sleep were found immediately after the lesion. Sleep gradually increased , but never returned to baseline Levels (baseline/month 1 post-lesion: waki ng, 30.6+/-4.58%/62.3+/-10.1%; S1, 5.1+/-0.74/3.9+/-1.91%; S2, 46.2+/-4.74% /23.1+/-5.47%; rapid eye movement sleep, 14.1+/-3.15%/7.2+/-5.42%). These c hanges are comparable in magnitude to those seen after basal forebrain lesi ons. Neuronal degeneration was found in the ventral rostral pens and midbra in, including the substantia nigra, ventral tegmental area, retrorubral nuc leus, and ventral mesencephalic and rostroventral pontine reticular formati on. We conclude that nuclei within the ventral mesencephalon and rostroventral pens play an important role in sleep regulation. (C) 1999 IBRO. Published b y Elsevier Science Ltd.