TY - JOUR
T1 - Epigenetic regulation of the circadian gene Per1 contributes to age-related changes in hippocampal memory
AU - Kwapis, Janine L.
AU - Alaghband, Yasaman
AU - Kramár, Enikö A.
AU - López, Alberto J.
AU - Vogel Ciernia, Annie
AU - White, André O.
AU - Shu, Guanhua
AU - Rhee, Diane
AU - Michael, Christina M.
AU - Montellier, Emilie
AU - Liu, Yu
AU - Magnan, Christophe N.
AU - Chen, Siwei
AU - Sassone-Corsi, Paolo
AU - Baldi, Pierre
AU - Matheos, Dina P.
AU - Wood, Marcelo A.
N1 - Funding Information:
We wish to thank all members of the Wood lab for scientific discussions and technical assistance. We would also like to acknowledge the University of California, Irvine Institute for Genomics and Bioinformatics High-Throughput Facility for help with RNA sequencing and Yuzo Kanomata for additional computing support. This work was supported by the National Institutes of Health grants (MH101491, AG051807, and AG050787 to M.A.W. and T32-AG000096-31, F32-AG052303, and K99-AG056596 to J.L.K.). The work of Y.L., C.M., S.C., and P.B. was in part supported by NSF grant IIS-1550705, DARPA grant D17AP00002, and NIH GM123558 to P.B. E. M. was supported by a long-term EMBO post-doctoral fellowship and an ARC Foundation award and work in the P.S.-C. lab was supported by grants from the National Institutes of Health, INSERM, and the Novo Nordisk Foundation Challenge Program.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85051860557&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85051860557&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-05868-0
DO - 10.1038/s41467-018-05868-0
M3 - Article
C2 - 30127461
AN - SCOPUS:85051860557
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3323
ER -