title: Neuroligin-1 links neuronal activity to sleep-wake regulation.
abstract: Maintaining wakefulness is associated with a progressive increase in the need for sleep. This phenomenon has been linked to changes in synaptic function. The synaptic adhesion molecule Neuroligin-1 (NLG1) controls the activity and synaptic localization of N-methyl-d-aspartate receptors, which activity is impaired by prolonged wakefulness. We here highlight that this pathway may underlie both the adverse effects of sleep loss on cognition and the subsequent changes in cortical synchrony. We found that the expression of specific Nlg1 transcript variants is changed by sleep deprivation in three mouse strains. These observations were associated with strain-specific changes in synaptic NLG1 protein content. Importantly, we showed that Nlg1 knockout mice are not able to sustain wakefulness and spend more time in nonrapid eye movement sleep than wild-type mice. These changes occurred with modifications in waking quality as exemplified by low theta/alpha activity during wakefulness and poor preference for social novelty, as well as altered delta synchrony during sleep. Finally, we identified a transcriptional pathway that could underlie the sleep/wake-dependent changes in Nlg1 expression and that involves clock transcription factors. We thus suggest that NLG1 is an element that contributes to the coupling of neuronal activity to sleep/wake regulation.
authors.affiliation: Department of Psychiatry, Université de Montréal, Montreal, QC, Canada H3C 3J7.
authors.forename: Janine
authors.initials: J
authors.lastname: El Helou
authors.forename: Erika
authors.initials: E
authors.lastname: Bélanger-Nelson
authors.forename: Marlène
authors.initials: M
authors.lastname: Freyburger
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dorsaz
authors.forename: Thomas
authors.initials: T
authors.lastname: Curie
authors.forename: Francesco
authors.initials: F
authors.lastname: La Spada
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Gaudreault
authors.forename: Éric
authors.initials: É
authors.lastname: Beaumont
authors.forename: Philippe
authors.initials: P
authors.lastname: Pouliot
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lesage
authors.forename: Marcos G
authors.initials: MG
authors.lastname: Frank
authors.forename: Paul
authors.initials: P
authors.lastname: Franken
authors.forename: Valérie
authors.initials: V
authors.lastname: Mongrain
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004569:Electroencephalography; D004576:Electromyography; D015870:Gene Expression; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012890:Sleep / Q000235:genetics / Q000502:physiology*; D012892:Sleep Deprivation / Q000235:genetics / Q000503:physiopathology; D013045:Species Specificity; D013997:Time Factors; D014851:Wakefulness / Q000235:genetics / Q000502:physiology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C093438:neuroligin 1
keywords: ChIP; EEG; gene expression; sleep homeostasis; synaptic plasticity