Epigenetic regulation of the circadian gene Per1 in the hippocampus mediates age-related changes in memory and synaptic plasticity

Kwapis, J. L.; Alaghband, Y.; Kramar, E. A.; Lopez, A. J.; Vogel Ciernia, A.; White, A. O.; Shu, G.; Rhee, D.; Michael, C. M.; Montellier, E.; Liu, Y.; Magnan, C. N.; Sassone-Corsi, P.; Baldi, P.; Matheos, D. P.; Wood, M. A.

doi:10.1101/301135

bioRxiv · 10.1101/301135

Epigenetic regulation of the circadian gene Per1 in the hippocampus mediates age-related changes in memory and synaptic plasticity

Kwapis, J. L.·Alaghband, Y.·Kramar, E. A.·Lopez, A. J.·Vogel Ciernia, A.·White, A. O.·Shu, G.·Rhee, D.·Michael, C. M.·Montellier, E.·Liu, Y.·Magnan, C. N.·Sassone-Corsi, P.·Baldi, P.·Matheos, D. P.·Wood, M. A.

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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 learning-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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Kwapis, J. L., Alaghband, Y., Kramar, E. A., Lopez, A. J., Vogel Ciernia, A., White, A. O., Shu, G., Rhee, D., Michael, C. M., Montellier, E., Liu, Y., Magnan, C. N., Sassone-Corsi, P., Baldi, P., Matheos, D. P., Wood, M. A.. 2018-04-13. Epigenetic regulation of the circadian gene Per1 in the hippocampus mediates age-related changes in memory and synaptic plasticity. https://doi.org/10.1101/301135

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