Suppression of preoptic sleep-regulatory neuronal activity during corticotropin-releasing factor-induced sleep disturbance.
Corticotropin releasing factor (CRF) is implicated in sleep and arousal regulation. Exogenous CRF causes sleep suppression that is associated with activation of at least two important arousal systems: pontine noradrenergic and hypothalamic orexin/hypocretin neurons. It is not known whether CRF also impacts sleep-promoting neuronal systems. We hypothesized that CRF-mediated changes in wake and sleep involve decreased activity of hypothalamic sleep-regulatory neurons localized in the preoptic area. To test this hypothesis, we examined the effects of intracerebroventricular administration of CRF on sleep-wake measures and c-Fos expression in GABAergic neurons in the median preoptic nucleus (MnPN) and ventrolateral preoptic area (VLPO) in different experimental conditions. Administration of CRF (0.1 nmol) during baseline rest phase led to delayed sleep onset and decreases in total amount and mean duration of non-rapid eye movement (NREM) sleep. Administration of CRF during acute sleep deprivation (SD) resulted in suppression of recovery sleep and decreased c-Fos expression in MnPN/VLPO GABAergic neurons. Compared with vehicle controls, intracerebroventricular CRF potentiated disturbances of both NREM and REM sleep in rats exposed to a species-specific psychological stressor, the dirty cage of a male conspecific. The number of MnPN/VLPO GABAergic neurons expressing c-Fos was reduced in the CRF-treated group of dirty cage-exposed rats. These findings confirm the involvement of CRF in wake-sleep cycle regulation and suggest that increased CRF signaling in the brain 1) negatively affects homeostatic responses to sleep loss, 2) exacerbates stress-induced disturbances of sleep, and 3) suppresses the activity of sleep-regulatory neurons of the MnPN and VLPO.
Research Service, Veterans Affairs Greater Los Angeles Healthcare System, North Hills, California; Departments of Medicine, University of California, Los Angeles, California; Ilia State University, Tbilisi, Georgia igvilia@ucla.edu.
Irma
I
Gvilia
Department of Psychology, University of California, Los Angeles, California; and.
Natalia
N
Suntsova
Research Service, Veterans Affairs Greater Los Angeles Healthcare System, North Hills, California;
Sunil
S
Kumar
Research Service, Veterans Affairs Greater Los Angeles Healthcare System, North Hills, California; Department of Psychology, University of California, Los Angeles, California; and.
Dennis
D
McGinty
Research Service, Veterans Affairs Greater Los Angeles Healthcare System, North Hills, California; Departments of Medicine, University of California, Los Angeles, California;
Ronald
R
Szymusiak
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012894:Sleep Stages / Q000187:drug effects*; D012893:Sleep Wake Disorders / Q000139:chemically induced / Q000378:metabolism*; D014851:Wakefulness / Q000187:drug effects
D003346:Corticotropin-Releasing Hormone
CRF; preoptic hypothalamus; sleep homeostasis; stress