Abstract
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.
Highlights
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
The mitogen-activated protein/ extracellular signal-regulated kinase (MEK) inhibition in heterozygous K-Ras knockout (KO) mice disrupt long-term potentiation and hippocampus-dependent long-term memory[34]. These studies indicate that the activation of the K-Ras–extracellular signal-regulated kinases (ERKs)– CREB pathway is required for the regulation of hippocampusdependent long-term memory
SCOP is rapidly degraded by calpain that is activated by Ca2 þ -influx in response to brain-derived neurotrophic factor (BDNF), KCl or N-methyl-D-aspartate (NMDA) treatment in cultured neurons, or to training for a hippocampus-dependent memory task[29]
Summary
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. A role of the master circadian clock in long-term memory formation was explored by lesioning the SCN, which caused arrhythmic locomotor activities in constant dark (DD) condition[41] (Supplementary Fig. 2a, upper panel). No significant variations were observed for SCOP and K-Ras levels in the whole hippocampal rafts (Fig. 3b), the CA1 rafts showed robust circadian oscillations in the amount of the two proteins, both peaking at CT16 (Fig. 3a), a peaking time of long-term recognition memory (Fig. 1b).
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