Abstract
Sleep slow waves are known to participate in memory consolidation, but slow waves also occur in anesthetized states, with no positive effect on memory. Here, we shed light onto this paradox, based on a combination of analysis of extracellular recordings in vitro and in in vivo and computational models. We find two types of slow waves, based on analyzing the temporal patterns of successive slow-wave events. The first type of slow waves is seen during sleep, while the second type appears to prevail in anesthetized states. Network models of spiking neurons predict that these two slow-wave dynamics correspond to different levels of spike-frequency adaptation in excitatory cells. This prediction was tested in vitro by varying adaptation strength using an agonist of acetylcholine receptors, which demonstrated a neuromodulatory switch between the two types of slow waves. Finally, we show that the first type of slow-wave dynamics is more sensitive to external stimuli, which can explain how slow waves in sleep and anesthesia differentially affect memory consolidation, as well as provide a link between slow-wave dynamics and memory diseases.
Significance statement During sleep, cortical neurons display slow oscillations, which are believed to participate in memory consolidation. However, it remains unknown why the apparently similar slow-wave dynamics seen under anesthesia do not produce the same effect on memory. Here, we show distinctive features of slow oscillatory patterns in sleep versus anesthesia, robust across species and anesthetics. Using computational modeling and in vitro preparations, we show that in anesthesia, depressed neuromodulation stabilizes neural dynamics, limits communication between neural assemblies, and can explain why memory encoding is prevented. Because the same neuromodulatory system is depressed in both anesthesia and Alzheimers disease, our results offer a mechanistic link between the sleep and memory symptoms of the disease, with implications for the identification of novel therapeutics.