SCOP/PHLPP1β mediates circadian regulation of long-term recognition memory

• Published in: Nature communications Vol. 7; no. 1; p. 12926
• Main Authors: Shimizu, Kimiko, Kobayashi, Yodai, Nakatsuji, Erika, Yamazaki, Maya, Shimba, Shigeki, Sakimura, Kenji, Fukada, Yoshitaka
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.09.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/89; 631/337; 631/378/1385/2640; 631/378/1595/2167; 631/378/1595/2638; 82; 82/51; 82/80; 96/95; Humanities and Social Sciences; multidisciplinary; Science
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms12926

Learning and memory depend on the time of day in various organisms, but it is not clear whether and how the circadian clock regulates memory performance. Here we show that consolidation of long-term recognition memory is a circadian-regulated process, which is blunted by disruption of the hippocampal clock. We focused on SCOP, a key molecule regulating hippocampus-dependent long-term memory for objects. The amounts of SCOP and its binding partner K-Ras in the hippocampal membrane rafts exhibit robust circadian changes, and SCOP knockdown in the hippocampal CA1 impairs long-term memory at night. Circadian changes in stimulus-dependent activation of ERK in the hippocampal neurons are dependent on the SCOP levels in the membrane rafts, while Scop knockout abrogates the activation rhythm. We conclude that long-term memory formation is regulated by the circadian clock through SCOP dynamics in the membrane rafts of the hippocampal CA1. Learning and memory are subject to circadian variation, though the molecular mechanisms behind this are unclear. Here, the authors show SCOP, a regulator of hippocampal memory, undergoes circadian changes in CA1 membrane raft dynamics and contributes to time-dependent changes in long-term memory.