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

  • Author(s): Kwapis, JL
  • Alaghband, Y
  • Kramár, EA
  • López, AJ
  • Vogel Ciernia, A
  • White, AO
  • Shu, G
  • Rhee, D
  • Michael, CM
  • Montellier, E
  • Liu, Y
  • Magnan, CN
  • Chen, S
  • Sassone-Corsi, P
  • Baldi, P
  • Matheos, DP
  • Wood, MA
  • et al.
Abstract

© 2018, The Author(s). 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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