title: Developmental ethanol exposure-induced sleep fragmentation predicts adult cognitive impairment.
abstract: Developmental ethanol (EtOH) exposure can lead to long-lasting cognitive impairment, hyperactivity, and emotional dysregulation among other problems. In healthy adults, sleep plays an important role in each of these behavioral manifestations. Here we explored circadian rhythms (activity, temperature) and slow-wave sleep (SWS) in adult mice that had received a single day of EtOH exposure on postnatal day 7 and saline littermate controls. We tested for correlations between slow-wave activity and both contextual fear conditioning and hyperactivity. Developmental EtOH resulted in adult hyperactivity within the home cage compared to controls but did not significantly modify circadian cycles in activity or temperature. It also resulted in reduced and fragmented SWS, including reduced slow-wave bout duration and increased slow-wave/fast-wave transitions over 24-h periods. In the same animals, developmental EtOH exposure also resulted in impaired contextual fear conditioning memory. The impairment in memory was significantly correlated with SWS fragmentation. Furthermore, EtOH-treated animals did not display a post-training modification in SWS which occurred in controls. In contrast to the memory impairment, sleep fragmentation was not correlated with the developmental EtOH-induced hyperactivity. Together these results suggest that disruption of SWS and its plasticity are a secondary contributor to a subset of developmental EtOH exposure's long-lasting consequences.
authors.affiliation: Department of Child and Adolescent Psychiatry, NYU School of Medicine, New York, NY, United States; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States. Electronic address: dwilson@nki.rfmh.org.
authors.forename: D A
authors.initials: DA
authors.lastname: Wilson
authors.affiliation: Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States.
authors.forename: K
authors.initials: K
authors.lastname: Masiello
authors.affiliation: Department of Child and Adolescent Psychiatry, NYU School of Medicine, New York, NY, United States; Sackler Neuroscience Graduate Program, NYU School of Medicine, New York, NY, United States.
authors.forename: M P
authors.initials: MP
authors.lastname: Lewin
authors.affiliation: Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States.
authors.forename: M
authors.initials: M
authors.lastname: Hui
authors.affiliation: Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States; Department of Psychiatry, NYU School of Medicine, New York, NY, United States.
authors.forename: J F
authors.initials: JF
authors.lastname: Smiley
authors.affiliation: Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States; Department of Psychiatry, NYU School of Medicine, New York, NY, United States.
authors.forename: M
authors.initials: M
authors.lastname: Saito
mesh_terms: D019973:Alcohol-Related Disorders / Q000503:physiopathology*; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002940:Circadian Rhythm / Q000502:physiology; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000503:physiopathology*; D003213:Conditioning, Psychological / Q000502:physiology; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005239:Fear / Q000502:physiology; D008568:Memory / Q000502:physiology; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D011379:Prognosis; D012890:Sleep / Q000502:physiology; D012892:Sleep Deprivation / Q000503:physiopathology*
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol
keywords: circadian rhythm; fetal alcohol disorder; insomnia; sleep fragmentation; slow-wave sleep