Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity

Sci Adv. 2023 Oct 27;9(43):eadj1010. doi: 10.1126/sciadv.adj1010. Epub 2023 Oct 25.

Abstract

The time of day strongly influences adaptive behaviors like long-term memory, but the correlating synaptic and molecular mechanisms remain unclear. The circadian clock comprises a canonical transcription-translation feedback loop (TTFL) strictly dependent on the BMAL1 transcription factor. We report that BMAL1 rhythmically localizes to hippocampal synapses in a manner dependent on its phosphorylation at Ser42 [pBMAL1(S42)]. pBMAL1(S42) regulates the autophosphorylation of synaptic CaMKIIα and circadian rhythms of CaMKIIα-dependent molecular interactions and LTP but not global rest/activity behavior. Therefore, our results suggest a model in which repurposing of the clock protein BMAL1 to synapses locally gates the circadian timing of plasticity.

MeSH terms

  • ARNTL Transcription Factors* / genetics
  • Circadian Clocks*
  • Circadian Rhythm / physiology
  • Hippocampus / metabolism
  • Phosphorylation

Substances

  • ARNTL Transcription Factors