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Sleep spindles promote hippocampal network downregulation during sleep
Niels Niethard1, Diego Marco Pagano2, Nima Mojtahedi2
1Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, 72076 Tübingen, Germany; Department of Cognitive Sciences, University of California, Irvine, Irvine, CA 92617, USA; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, University Tübingen (IDM), 72076 Tübingen, Germany.
Current Biology : CB
|February 28, 2026
Summary
During sleep, hippocampal neuron activity gradually decreases, especially after sleep spindles and REM sleep. This progressive downregulation supports memory consolidation.
Area of Science:
- Neuroscience
- Sleep Research
- Memory Consolidation
Background:
- Sleep is believed to downregulate neural activity and synaptic connections strengthened during wakefulness.
- Simultaneously, sleep enhances activity in brain networks crucial for consolidating hippocampus-dependent episodic memories.
- Understanding these dynamic processes in hippocampal networks during natural sleep is essential.
Purpose of the Study:
- To investigate the changes in hippocampal CA1 neuronal activity during natural sleep in mice.
- To correlate neuronal activity patterns with electroencephalogram (EEG) markers of sleep, such as slow oscillations (SOs) and spindles.
- To elucidate the mechanisms underlying sleep-dependent memory processing in the hippocampus.
Main Methods:
- Combined two-photon calcium (Ca2+) imaging of hippocampal CA1 neuronal activity in mice.
- Simultaneous electroencephalogram (EEG) recordings to identify sleep stages (slow-wave sleep [SWS] and rapid eye movement [REM] sleep) and track slow oscillations (SOs) and spindles.
- Analysis of neuronal activity changes across consecutive sleep epochs and in relation to specific sleep events.
Main Results:
- The number of active hippocampal neurons increased from wakefulness into sleep, peaking during REM sleep.
- A gradual, persistent downregulation of Ca2+ signaling was observed across consecutive SWS epochs, particularly in neurons active in the prior epoch.
- This downregulation was more pronounced when SWS epochs were separated by REM sleep, and sleep spindle density predicted the extent of downregulation. Spindle onsets rapidly reduced neuronal activity.
Conclusions:
- Hippocampal network activity does not uniformly decrease during individual sleep epochs but shows progressive downregulation across SWS.
- A spindle-associated mechanism, interacting with intermittent REM sleep, drives this progressive downregulation.
- This process is crucial for supporting systems memory consolidation during sleep.
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