Serotonin modulates infraslow oscillation in the dentate gyrus during Non-REM sleep

Abstract

The importance of sleep in memory consolidation is well-established, with the hippocampal CA1 and CA3 subregions playing a crucial role in this process. The current working hypothesis postulates that episodic memory traces captured during waking hours are replayed in the hippocampal CA1-CA3 areas and transferred to the cortex for long-term storage during sleep. While the entorhinal cortex provides sensory and spatial information primarily to the hippocampus via the dentate gyrus (DG), the DG has traditionally been regarded as a "silent partner" in memory consolidation. The transfer of captured memory traces from the DG to downstream hippocampal areas remains largely unknown. To investigate this, we used optical imaging tools to record neural activity in the DG during different sleep stages. Strikingly, we found that many of the DG cells are even more active during sleep than wakefulness and the populational activity in the DG slowly oscillates during non-REM (NREM) sleep. The cycles of this oscillatory activity coincided with microarousals and were tightly locked to brief serotonin (5-HT) bursts during NREM sleep. Pharmacological blockade of 5-HT1a receptors abolished the calcium oscillations in the DG. Furthermore, the genetic knockdown of 5-HT1a receptors in the DG lead to memory impairment in spatial and contextual memory tasks. Together, our findings suggest that serotonin-driven infraslow calcium oscillations in the DG during NREM sleep are necessary for memory consolidation.

Ultraslow serotonin oscillations in the hippocampus delineate substates across NREM and waking

“…Importantly, in both studies, these substates were delineated by the phase of ultraslow oscillations (< 0.1 Hz) of sigma power and noradrenaline levels, respectively. While NREM substates have not yet been examined in relation to 5-HT levels, ultra-slow oscillations have been observed in population activity in the Dorsal Raphe Nucleus (DRN) (7,8), as well as in extracellular 5-HT levels in the hippocampal dentate gyrus (9) during NREM, suggesting that 5-HT may also distinguish pro-arousal and pro-memory substates.…”