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 lo-calizes 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.
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Barone, I., Gilette, N. M., Hawks-Mayer, H., Handy, J., Zhang, K. J., Chifamba, F. F., … Lipton, J. O. (2023). Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity. Science Advances, 9(43). https://doi.org/10.1126/SCIADV.ADJ1010