A Serotonin-Modulated Circuit Controls Sleep Architecture to Regulate Cognitive Function Independent of Total Sleep in Drosophila

Abstract

Both the structure and the amount of sleep are important for brain function. Entry into deep, restorative stages of sleep is time dependent; short sleep bouts selectively eliminate these states. Fragmentation-induced cognitive dysfunction is a feature of many common human sleep pathologies. Whether sleep structure is normally regulated independent of the amount of sleep is unknown. Here, we show that in Drosophila melanogaster, activation of a subset of serotonergic neurons fragments sleep without major changes in the total amount of sleep, dramatically reducing long episodes that may correspond to deep sleep states. Disruption of sleep structure results in learning deficits that can be rescued by pharmacologically or genetically consolidating sleep. We identify two reciprocally connected sets of ellipsoid body neurons that form the heart of a serotoninmodulated circuit that controls sleep architecture. Taken together, these findings define a circuit essential for controlling the structure of sleep independent of its amount.

Covert sleep-related biological processes are revealed by probabilistic analysis in Drosophila

“…Our results indicate that fragmented sleep can be the result of decreased sleep depth [i.e., high P(Wake)], increased sleep pressure [i.e., high P(Doze)] or a combination of the two. In line with this, we have recently shown that activation of serotonergic neurons that fragment sleep without changing its total amount primarily increases P(Doze) (48). Biologically, this may make sense.…”

“…Rousing the flies is likely to disrupt the deeper-sleep substates found in longer-sleep episodes (24). Repeated rousing may activate homeostatic mechanisms that alter sleep depth (18), and fragmentation of sleep without sleep loss can even trigger sleep rebound (48). Finally, the arousing stimulus may act as a Zeitgeber to the circadian system (49).…”

Modulation of sleep-courtship balance by nutritional status inDrosophila

“…Sleep is strongly influenced by monoaminergic neuromodulators, including dopamine, serotonin, and octopamine and its mammalian analog norepinephrine (Griffith, 2013; Joiner, 2016; Liu et al, 2019; Nall and Sehgal, 2014; Ni et al, 2019; Singh et al, 2015). We previously showed that octopamine is a significant mediator of sleep suppression by male sex drive upstream of P1 neurons (Machado et al, 2017).…”

A neural signature of choice under sensory conflict inDrosophila

“…The mushroom body is an insect central brain region involved in gustatory learning and memory 19,20 and valence encoding 21 , and is thought to be a major center controlling higher-order behaviors [22][23][24] . The insect central complex is an evolutionarily conserved central brain region whose ellipsoid body and protocerebral bridge sub-regions have been implicated in navigation [25][26][27][28][29][30][31][32] and sleep [33][34][35] . The central complex fan-shaped body, a laminar neural sub-region, has been implicated in sleep [36][37][38][39] and ethanol preference 40,41 .…”