title: A role for cortical nNOS/NK1 neurons in coupling homeostatic sleep drive to EEG slow wave activity.
abstract: Although the neural circuitry underlying homeostatic sleep regulation is little understood, cortical neurons immunoreactive for neuronal nitric oxide synthase (nNOS) and the neurokinin-1 receptor (NK1) have been proposed to be involved in this physiological process. By systematically manipulating the durations of sleep deprivation and subsequent recovery sleep, we show that activation of cortical nNOS/NK1 neurons is directly related to non-rapid eye movement (NREM) sleep time, NREM bout duration, and EEG δ power during NREM sleep, an index of preexisting homeostatic sleep drive. Conversely, nNOS knockout mice show reduced NREM sleep time, shorter NREM bouts, and decreased power in the low δ range during NREM sleep, despite constitutively elevated sleep drive. Cortical NK1 neurons are still activated in response to sleep deprivation in these mice but, in the absence of nNOS, they are unable to up-regulate NREM δ power appropriately. These findings support the hypothesis that cortical nNOS/NK1 neurons translate homeostatic sleep drive into up-regulation of NREM δ power through an NO-dependent mechanism.
authors.affiliation: Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA 94025.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Morairty
authors.forename: Lars
authors.initials: L
authors.lastname: Dittrich
authors.forename: Ravi K
authors.initials: RK
authors.lastname: Pasumarthi
authors.forename: Daniel
authors.initials: D
authors.lastname: Valladao
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Heiss
authors.forename: Dmitry
authors.initials: D
authors.lastname: Gerashchenko
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kilduff
mesh_terms: D000818:Animals; D058256:Brain Waves / Q000502:physiology*; D002452:Cell Count; D002540:Cerebral Cortex / Q000502:physiology*; D004569:Electroencephalography; D004576:Electromyography; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism*; D051379:Mice; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000502:physiology*
chemical_list: D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse
keywords: Fos; Nos1; cerebral cortex; interneurons; sleep homeostasis