A time window for memory consolidation during NREM sleep revealed by cAMP oscillation

  • Neuron. 2025 Jun 18;113(12):1983-1997.e7. doi: 10.1016/j.neuron.2025.03.020.
Ziru Deng  1 ,  Xiang Fei  2 ,  Siyu Zhang  3 ,  Min Xu  4
Affiliations
  • 1. Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China; Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 2. Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 3. Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China; Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: [email protected].
  • 4. Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: [email protected].
PMID: 40233747 DOI: 10.1016/j.neuron.2025.03.020
Abstract

Memory formation requires specific neural activity in coordination with intracellular signaling mediated by second messengers such as cyclic adenosine monophosphate (cAMP). However, the real-time dynamics of cAMP remain largely unknown. Here, using a genetically encoded cAMP sensor with high temporal resolution, we found neural-activity-dependent rapid cAMP elevation during learning. Interestingly, in slow-wave sleep, during which memory consolidation occurs, the cAMP level in mice was anti-correlated with neural activity and exhibited norepinephrine β1 receptor-dependent infra-slow oscillations that were synchronized across the hippocampus and cortex. Furthermore, the hippocampal-cortical interactions increased during the narrow time-window of the peak cAMP level; suppressing hippocampal activity specifically during this window impaired spatial memory consolidation. Thus, hippocampal-dependent memory consolidation occurs within a specific time window of high cAMP activity during slow-wave sleep.

Keywords
cAMP; hippocampus; memory; memory consolidation; norepinephrine; plasticity; sleep.
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