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Open Access Publications from the University of California

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

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

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.

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