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

Nat Commun. 2018 Aug 20;9(1):3323. doi: 10.1038/s41467-018-05868-0.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aging / physiology*
  • Animals
  • Circadian Rhythm / genetics*
  • Epigenesis, Genetic*
  • Gene Deletion
  • Gene Knockdown Techniques
  • Hippocampus / physiology*
  • Histone Deacetylases / metabolism
  • Long-Term Potentiation
  • Memory / physiology*
  • Memory Disorders / genetics
  • Memory Disorders / physiopathology
  • Mice, Inbred C57BL
  • Neuronal Plasticity / genetics
  • Period Circadian Proteins / genetics*
  • Period Circadian Proteins / metabolism


  • Per1 protein, mouse
  • Period Circadian Proteins
  • Histone Deacetylases
  • histone deacetylase 3