Epigenetic regulation of the circadian gene Per1 contributes to age-related changes in hippocampal memory

Janine L. Kwapis, Yasaman Alaghband, Enikö A. Kramár, Alberto J. López, Annie Vogel Ciernia, André O. White, Guanhua Shu, Diane Rhee, Christina M. Michael, Emilie Montellier, Yu Liu, Christophe N. Magnan, Siwei Chen, Paolo Sassone-Corsi, Pierre Baldi, Dina P. Matheos, Marcelo A. Wood

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Aging is accompanied by impairments in both circadian rhythmicity and long-term memory. Although it is clear that memory performance is affected by circadian cycling, it is unknown whether age-related disruption of the circadian clock causes impaired hippocampal memory. Here, we show that the repressive histone deacetylase HDAC3 restricts long-term memory, synaptic plasticity, and experience-induced expression of the circadian gene Per1 in the aging hippocampus without affecting rhythmic circadian activity patterns. We also demonstrate that hippocampal Per1 is critical for long-term memory formation. Together, our data challenge the traditional idea that alterations in the core circadian clock drive circadian-related changes in memory formation and instead argue for a more autonomous role for circadian clock gene function in hippocampal cells to gate the likelihood of long-term memory formation.

Original languageEnglish (US)
Article number3323
JournalNature communications
Issue number1
StatePublished - Dec 1 2018

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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