title: Sleep protects excitatory cortical circuits against oxidative damage.
abstract: Activity in excitatory cortical pathways increases the oxidative metabolism of the brain and the risk of oxidative damage. Oxyradicals formed during periods of activity are mopped up by neural pools of nuclear factor kappa-B resulting in their activation and translocation to cell nuclei. During waking hours, glucocorticoids inhibit transactivation by nuclear factor kappa-B, increase central norepinephrine release, and elevate expression of prostaglandin D2. The build-up of nuclear factor kappa-B and prostaglandin D2 produces sleep pressures leading to sleep onset, normally gated by circadian melatonin release. During slow wave sleep nuclear factor kappa-B induces transcription of synaptogenic and antioxidant products and synaptic remodeling follows. Synaptically remodeled neural circuits have modified conductivity patterns and timescales and need to be resynchronized with existing unmodified neural circuits. The resynchronization process, mediated by theta rhythm, occurs during rapid eye movement sleep and is orchestrated from pontine centers. Resynchronization of remodeled neural circuits produces dreams. The waking state results upon successful resynchronization. Rapid eye movement sleep deprivation results in a lack of resynchronization and leads to cognitive inefficiencies. The model presented here proposes that the primary purpose of sleep is to protect cortical circuits against oxidative damage by reducing cortical activity and by remodeling and resynchronizing cortical circuits during this period of reduced activity to sustain new patterns of activation more effectively.
authors.affiliation: Department of Psychology, The University of British Columbia, 2136 West Mall, Vancouver, BC, Canada V6T 1Z4. schulze@interchange.ubc.ca
authors.forename: Georg
authors.initials: G
authors.lastname: Schulze
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology; D004325:Dreams / Q000502:physiology; D005938:Glucocorticoids / Q000378:metabolism; D008550:Melatonin / Q000378:metabolism; D008959:Models, Neurological; D016328:NF-kappa B / Q000378:metabolism; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
chemical_list: D005938:Glucocorticoids; D016328:NF-kappa B; D008550:Melatonin