title: Neurotoxic N-methyl-D-aspartate lesion of the ventral midbrain and mesopontine junction alters sleep-wake organization.
abstract: The dorsal regions of the midbrain and pons have been found to participate in sleep regulation. However, the physiological role of the ventral brainstem in sleep regulation remains unclear. We used N-methyl-D-aspartate-induced lesions of the ventral midbrain and pons to address this question. Unlike dorsal mesencephalic reticular formation lesions, which produce somnolence and electroencephalogram synchronization, we found that ventral midbrain lesions produce insomnia and hyperactivity. Marked increases in waking and decreases in slow wave sleep stage 1 (S1), stage 2 (S2) and rapid eye movement sleep were found immediately after the lesion. Sleep gradually increased, but never returned to baseline levels (baseline/month 1 post-lesion: waking, 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 changes are comparable in magnitude to those seen after basal forebrain lesions. Neuronal degeneration was found in the ventral rostral pons and midbrain, including the substantia nigra, ventral tegmental area, retrorubral nucleus, and ventral mesencephalic and rostroventral pontine reticular formation. We conclude that nuclei within the ventral mesencephalon and rostroventral pons play an important role in sleep regulation.
authors.affiliation: Department of Psychiatry, School of Medicine UCLA, and VAMC, Sepulveda, CA 91343, USA.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Lai
authors.forename: T
authors.initials: T
authors.lastname: Shalita
authors.forename: T
authors.initials: T
authors.lastname: Hajnik
authors.forename: J P
authors.initials: JP
authors.lastname: Wu
authors.forename: J S
authors.initials: JS
authors.lastname: Kuo
authors.forename: L G
authors.initials: LG
authors.lastname: Chia
authors.forename: J M
authors.initials: JM
authors.lastname: Siegel
mesh_terms: D000818:Animals; D001931:Brain Mapping; D001933:Brain Stem / Q000502:physiology; D002415:Cats; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D004585:Electrooculography / Q000187:drug effects; D005260:Female; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009043:Motor Activity; D016202:N-Methylaspartate / Q000633:toxicity*; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009498:Neurotoxins / Q000633:toxicity; D009928:Organ Specificity; D011149:Pons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D016548:Prosencephalon / Q000502:physiology; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*
chemical_list: D009498:Neurotoxins; D016202:N-Methylaspartate