Abnormal circadian oscillation of hippocampal MAPK activity and power spectrums in NF1 mutant mice

Studies have implied that the circadian oscillation of mitogen-activated protein kinase (MAPK) signal pathways is crucial for hippocampus-dependent memory. NF1 mouse models (Nf1 heterozygous null mutants; Nf1 ^+/-) displayed enhanced MAPK activity in the hippocampus and resulted in memory deficits. We assumed a link between MAPK pathways and hippocampal rhythmic oscillations, which have never been explored in Nf1 ^+/- mice. We demonstrated that the level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation in Nf1 ^+/- mice were significantly higher at nighttime than at daytime. Moreover, the in vivo recording revealed that for the Nf1 ^+/- group, the power spectral density of theta rhythm significantly decreased and the firing rates of pyramidal neurons increased. Our results indicated that the hippocampal MAPK oscillation and theta rhythmic oscillations in Nf1 ^+/- mice were disturbed and hinted about a possible mechanism for the brain dysfunction in Nf1 ^+/- mice.