A paradoxical impact of alcohol on sleep-memory coupling

Sleep serves a fundamental role in memory consolidation, but this can be influenced by physiological context. For instance, satiated Drosophila require sleep for appetitive memory consolidation, but starved flies that must forage for food switch to sleep-independent memory. As ethanol intoxication alters behaviors such as sleep and memory, we asked how it affects the role of sleep in memory consolidation. Here, we demonstrate that acute ethanol inverts the canonical link between sleep and memory in Drosophila. Ethanol selectively impairs memory consolidation in satiated flies by causing a switch to sleep-independent memory, which then cannot be supported because of ethanol-induced sedation. Under these conditions, sleep deprivation rescues memory and requires the upregulation of neuropeptide F (NPF), which signals through NPF receptors on PPL1 dopaminergic neurons. We suggest that reward-seeking behaviors, induced by starvation or ethanol, invoke sleep-independent memory. However, ethanol has a paradoxical impact, wherein it induces a switch to sleep-independent memory but concurrently promotes sedation, thereby causing sleep to become detrimental to memory consolidation.