biostudies-literatureCooper CBundesministerium für Bildung und ForschungDeutsche ForschungsgemeinschaftEuropean Research CouncilRP101105https://www.ebi.ac.uk/biostudies/studies/S-EPMC12252544biostudies-literatureUnknown13Beyond the vast array of functional roles attributed to serotonin (5-HT) in the brain, changes in 5-HT levels have been shown to accompany changes in behavioral states, including WAKE, NREM, and REM sleep. Whether 5-HT dynamics at shorter time scales can be seen to delineate substates within these larger brain states remains an open question. Here, we performed simultaneous recordings of extracellular 5-HT using a recently developed G-Protein-Coupled Receptor-Activation-Based 5-HT sensor (GRAB5-HT3.0) and local field potential in the hippocampal CA1 of mice, which revealed the presence of prominent ultraslow (<0.05 Hz) 5-HT oscillations both during NREM and WAKE states. Interestingly, the phase of these ultraslow 5-HT oscillations was found to distinguish substates both within and across leLifeUltraslow serotonin oscillations in the hippocampus delineate substates across NREM and waking.PMC1225254410.3030/810580431572356327654276Exc-2049-39068808701GQ1420B184695641Tukker JJTritsch NSchmitz DCooper CParthier DSibille JfalseUltraslow serotonin oscillations in the hippocampus delineate substates across NREM and waking.Beyond the vast array of functional roles attributed to serotonin (5-HT) in the brain, changes in 5-HT levels have been shown to accompany changes in behavioral states, including WAKE, NREM, and REM sleep. Whether 5-HT dynamics at shorter time scales can be seen to delineate substates within these larger brain states remains an open question. Here, we performed simultaneous recordings of extracellular 5-HT using a recently developed G-Protein-Coupled Receptor-Activation-Based 5-HT sensor (GRAB5-HT3.0) and local field potential in the hippocampal CA1 of mice, which revealed the presence of prominent ultraslow (<0.05 Hz) 5-HT oscillations both during NREM and WAKE states. Interestingly, the phase of these ultraslow 5-HT oscillations was found to distinguish substates both within and across l2025-01-01T00:00:00Z2025 Jul2026-03-27T17:07:17.872Z2025-08-28T03:09:16.502ZS-EPMC122525444064357210.7554/eLife.101105