Circadian Regulation by REV-ERB alpha Mediates Hippocampal E-LTP in a Time-dependent Manner

Abstract

Circadian rhythms are driven by circadian oscillators, and these rhythms result in the biological phenomenon of 24-h oscillations. Previous studies suggest that learning and memory are affected by circadian rhythms. One of the genes responsible for generating the circadian rhythm is Rev-ERB alpha. The REV-ERB alpha protein is a nuclear receptor that acts as a transcriptional repressor, and is a core component of the circadian clock. However, the role of REV-ERB alpha in neurophysiological processes in the hippocampus has not been characterized yet. In this study, we examined the time-dependent role of REV-ERB alpha in hippocampal synaptic plasticity using Rev-ERB alpha KO mice. The KO mice lacking REV-ERB alpha displayed abnormal NMDAR-dependent synaptic potentiation (E-LTP) at CT12 similar to CT14 (subjective night) when compared to their wild-type littermates. However, Rev-ERB alpha KO mice exhibited normal E-LTP at CT0 similar to CT2 (subjective day). We also found that the Rev-ERB alpha KO mice had intact late LTP (L-LTP) at both subjective day and night. Taken together, these results provide evidence that REV-ERB alpha is critical for hippocampal E-LTP during the dark period.