title: Optogenetic disruption of sleep continuity impairs memory consolidation.
abstract: Memory consolidation has been proposed as a function of sleep. However, sleep is a complex phenomenon characterized by several features including duration, intensity, and continuity. Sleep continuity is disrupted in different neurological and psychiatric conditions, many of which are accompanied by memory deficits. This finding has raised the question of whether the continuity of sleep is important for memory consolidation. However, current techniques used in sleep research cannot manipulate a single sleep feature while maintaining the others constant. Here, we introduce the use of optogenetics to investigate the role of sleep continuity in memory consolidation. We optogenetically targeted hypocretin/orexin neurons, which play a key role in arousal processes. We used optogenetics to activate these neurons at different intervals in behaving mice and were able to fragment sleep without affecting its overall amount or intensity. Fragmenting sleep after the learning phase of the novel object recognition (NOR) task significantly decreased the performance of mice on the subsequent day, but memory was unaffected if the average duration of sleep episodes was maintained at 62-73% of normal. These findings demonstrate the use of optogenetic activation of arousal-related nuclei as a way to systematically manipulate a specific feature of sleep. We conclude that regardless of the total amount of sleep or sleep intensity, a minimal unit of uninterrupted sleep is crucial for memory consolidation.
authors.affiliation: Departments of Psychiatry and Behavioral Science and Biology, Stanford University, Stanford, CA 94305-5020, USA.
authors.forename: Asya
authors.initials: A
authors.lastname: Rolls
authors.forename: Damien
authors.initials: D
authors.lastname: Colas
authors.forename: Antoine
authors.initials: A
authors.lastname: Adamantidis
authors.forename: Matt
authors.initials: M
authors.lastname: Carter
authors.forename: Tope
authors.initials: T
authors.lastname: Lanre-Amos
authors.forename: H Craig
authors.initials: HC
authors.lastname: Heller
authors.forename: Luis
authors.initials: L
authors.lastname: de Lecea
mesh_terms: D000818:Animals; D004569:Electroencephalography; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008568:Memory / Q000502:physiology* / Q000528:radiation effects; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D000068797:Orexins; D010812:Physical Stimulation; D012890:Sleep / Q000235:genetics* / Q000528:radiation effects*; D012892:Sleep Deprivation / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D012895:Sleep, REM / Q000502:physiology / Q000528:radiation effects; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology; D013647:Task Performance and Analysis; D013997:Time Factors
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins