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Significance SHARP1 and SHARP2 transcription factors are modulators of the sleep/wake homeostasis. Sleep is thought to be important for efficient memory consolidation by gradual stabilization of hippocampus-dependent memory traces in stable cortical modules. Here, SHARP1 and SHARP2 single and double null mutant mice were investigated in cognitive processing. SHARP1 and SHARP2 double null mutants show enhanced cortex-dependent remote fear memory formation, although hippocampus-dependent recent fear memory formation is not changed. Molecular analyses revealed that insulin-related growth factor 2 (IGF2)/MAPK signaling is elevated in the cortex of double mutants and that IGF2 overexpression in the anterior cingulate cortex is sufficient to enhance fear memory consolidation. Our analyses provide evidence that the control of sleep and memory consolidation may share common molecular mechanisms.

Enhanced memory consolidation in mice lacking the circadian modulators Sharp1 and -2 caused by elevated Igf2 signaling in the cortex