We show that changes in dopamine levels differentially affect arousal for behaviors of varying complexity. Complex behaviors, such as visual perception, degenerate when dopamine levels are either too high or too low, in accordance with the inverted-U hypothesis of dopamine action in the mammalian brain. Simpler behaviors, such as sleep and locomotion, show graded responses that follow changes in dopamine level.

Optogenetic upregulation of cyclic adenosine monophosphate during the day increases sleep intensity at night, whereas loss of function of a molecule involved in synaptic pruning, the fragile-X mental retardation protein, increases sleep intensity during the day. Our results show that sleep is not homogenous in insects, and suggest that waking behavior and the associated synaptic plasticity mechanisms determine the timing and intensity of deep sleep stages in Drosophila.

SUMMARY Given the role that sleep plays in modulating plasticity, we hypothesized that increasing sleep would restore memory to canonical memory mutants without specifically rescuing the causal molecular-lesion. Sleep was increased using three independent strategies: activating the dorsal Fan Shaped Body (FB), increasing the expression of Fatty acid binding protein (dFabp) or by administering the GABA-A agonist 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol (THIP). Short-term memory (STM) or Long-term memory (LTM) was evaluated in rutabaga (rut) and dunce (dnc) mutants using Aversive Phototaxic Suppression (APS) and courtship conditioning. Each of the three independent strategies increased sleep and restored memory to rut and dnc mutants. Importantly, inducing sleep also reverses memory defects in a Drosophila model of Alzheimer’s disease. Together these data demonstrate that sleep plays a more fundamental role in modulating behavioral plasticity than previously appreciated and suggests that increasing sleep may benefit patients with certain neurological disorders.

Extended periods of rest in Drosophila melanogaster resemble mammalian sleep states in that they are characterized by heightened arousal thresholds and specific alterations in gene expression. Defined as inactivity periods spanning 5 or more min, amounts of this sleep-like state are, as in mammals, sensitive to prior amounts of waking activity, time of day, and pharmacological intervention. Clearly recognizable changes in the pattern and amount of brain electrical activity accompany changes in motor activity and arousal thresholds originally used to identify mammalian sleeping behavior. Electroencephalograms (EEGs) and/or local field potentials (LFPs) are now widely used to quantify sleep state amounts and define types of sleep. Thus, slow-wave sleep (SWS) is characterized by EEG spindles and large-amplitude delta-frequency (0-3.5 Hz) waves. Rapid-eye movement (REM) sleep is characterized by irregular gamma-frequency cortical EEG patterns and rhythmic theta-frequency (5-9 Hz) hippocampal EEG activity. It is unknown whether rest and activity in Drosophila are associated with distinct electrophysiological correlates. To address this issue, we monitored motor activity levels and recorded LFPs in the medial brain between the mushroom bodies, structures implicated in the modulation of locomotor activity, of Drosophila. The results indicate that LFPs can be reliably recorded from the brains of awake, moving fruit flies, that targeted genetic manipulations can be used to localize sources of LFP activity, and that brain electrical activity of Drosophila is reliably correlated with activity state.