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 and Marcelo A. Wood ()
Additional contact information
Janine L. Kwapis: University of California
Yasaman Alaghband: University of California
Enikö A. Kramár: University of California
Alberto J. López: University of California
Annie Vogel Ciernia: University of California
André O. White: Mount Holyoke College
Guanhua Shu: University of California
Diane Rhee: University of California
Christina M. Michael: University of California
Emilie Montellier: University of California
Yu Liu: University of California
Christophe N. Magnan: University of California
Siwei Chen: University of California
Paolo Sassone-Corsi: University of California
Pierre Baldi: University of California
Dina P. Matheos: University of California
Marcelo A. Wood: University of California

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-05868-0

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