Genetic disruption of circadian rhythms impairs hippocampus-dependent memory

Abstract

Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock for memory. Bmal1-/- mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer collateral/commisurral-CA1 synapse, and signal transduction activity in the hippocampus. Bmal1-/- mice exhibited impaired contextual fear and spatial memory. Furthermore, LTP in hippocampal slices from Bmal1-/- mice was also significantly decreased relative to wildtype mice. Activation of Erk1,2 MAP kinase (MAPK) during training for contextual fear memory and diurnal oscillation of MAPK activity and cAMP in the hippocampus were also lost in Bmal1-/- mice, suggesting that the memory defects were due to loss of the memory consolidation pathway in the hippocampus. We conclude that critical signaling events in the hippocampus required for memory depend on BMAL1, however BMAL1 is not required in area CA1 of the hippocampus.