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.nonrapid eye movement sleep | rapid eye movement sleep A lthough much has been learned about how sleep is regulated, there is still no consensus on the function of sleep. One hypothesis is that sleep is needed for memory consolidation (1-5). Testing this hypothesis has been confounded by sleep deprivation methodologies which are drastic manipulations affecting the overall activity of neuronal networks, including cellular energy demand (6, 7), protein synthesis (8), levels of free radicals (9), and specific synaptic changes (10). In many cases sleep deprivation also induces a stress response (11, 12), which itself has been shown to affect memory (4, 13).Some argue that sleep might support memory consolidation by merely providing passive isolation from sensory interruption (14, 15), a claim that cannot be excluded when external sensory stimulation (such as gentle handling or playing a tone) is the method used to disturb sleep. Traditional methods of sleep deprivation disrupt the composition of sleep [percentage of rapid eye movement (REM) and non-REM (NREM) sleep] at the same time as disrupting sleep quality, sleep continuity, and, in most cases, reducing total sleep duration (8,16,17). Thus, it has not been possible to study the role of a specific characteristic of sleep, such as sleep continuity, in memory consolidation.Sleep continuity is affected by different neurological conditions, e.g., sleep apnea, aging, and alcoholism (18,19). The occurrence of memory deficits in many of these conditions raised the question of whether the conti...

Animal Studies on the Role of Sleep in Memory: From Behavioral Performance to Molecular Mechanisms

“…Using an optogenetic approach to wake up mice by activating orexin/hypocretin neurons, the laboratory of de Lecea recently found that the consolidation of memories for object identity is attenuated by sleep fragmentation during the first 4 h after training (Rolls et al 2011). When the average duration of sleep episodes was maintained at around 70 % of normal, the memory for the object identity was unaffected.…”

Sleeping on the wing

“…Indeed, even when sleeping in flight, sleep was more fragmented and less deep than sleep on land. In contrast with frigatebirds, in animals ranging from insects [92] to humans [93], far shorter periods of sleep restriction and fragmentation [94] have profound adverse effects on their ability to maintain wakefulness and interact adaptively with the environment. People fall asleep while driving a car after losing just a few hours of sleep, even when aware of the dangers and trying to keep themselves awake.…”

Sleep Apnea Research in Animals. Past, Present, and Future

“…Subsequently, they showed that optic stimulation (once every 60 s) caused frequent, brief arousals, without altering the total sleep time or architecture. After 4 hours of this stimulus, mice exhibited deficits in memory consolidation (68).…”