title: Loss of Gnas imprinting differentially affects REM/NREM sleep and cognition in mice.
abstract: It has been suggested that imprinted genes are important in the regulation of sleep. However, the fundamental question of whether genomic imprinting has a role in sleep has remained elusive up to now. In this work we show that REM and NREM sleep states are differentially modulated by the maternally expressed imprinted gene Gnas. In particular, in mice with loss of imprinting of Gnas, NREM and complex cognitive processes are enhanced while REM and REM-linked behaviors are inhibited. This is the first demonstration that a specific overexpression of an imprinted gene affects sleep states and related complex behavioral traits. Furthermore, in parallel to the Gnas overexpression, we have observed an overexpression of Ucp1 in interscapular brown adipose tissue (BAT) and a significant increase in thermoregulation that may account for the REM/NREM sleep phenotypes. We conclude that there must be significant evolutionary advantages in the monoallelic expression of Gnas for REM sleep and for the consolidation of REM-dependent memories. Conversely, biallelic expression of Gnas reinforces slow wave activity in NREM sleep, and this results in a reduction of uncertainty in temporal decision-making processes.
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
authors.forename: Glenda
authors.initials: G
authors.lastname: Lassi
authors.forename: Simon T
authors.initials: ST
authors.lastname: Ball
authors.forename: Silvia
authors.initials: S
authors.lastname: Maggi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Colonna
authors.forename: Thierry
authors.initials: T
authors.lastname: Nieus
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cero
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bartolomucci
authors.forename: Jo
authors.initials: J
authors.lastname: Peters
authors.forename: Valter
authors.initials: V
authors.lastname: Tucci
mesh_terms: D002001:Adipose Tissue, Brown; D000483:Alleles; D000818:Animals; D001831:Body Temperature; D001833:Body Temperature Regulation / Q000235:genetics / Q000502:physiology; D002864:Chromogranins; D003071:Cognition / Q000502:physiology*; D019175:DNA Methylation; D004569:Electroencephalography; D005091:Exons; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation; D018392:Genomic Imprinting; D007473:Ion Channels; D051379:Mice; D024101:Mitochondrial Proteins; D017384:Sequence Deletion; D012895:Sleep, REM / Q000235:genetics* / Q000502:physiology*; D000071256:Uncoupling Protein 1; D014851:Wakefulness
chemical_list: D002864:Chromogranins; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C498642:Gnas protein, mouse; D019205:GTP-Binding Protein alpha Subunits, Gs