title: Genetic disruption of the core circadian clock 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 in memory. Bmal1-/- mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippocampus. Bmal1-/- mice exhibit impaired contextual fear and spatial memory. Furthermore, LTP in hippocampal slices from Bmal1-/- mice is also significantly decreased relative to that from wild-type 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 is also lost in Bmal1-/- mice, suggesting that the memory defects are due to reduction of the memory consolidation pathway in the hippocampus. We conclude that critical signaling events in the hippocampus required for memory depend on BMAL1.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195-7750, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Wardlaw
authors.affiliation: Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195-7750, USA.
authors.forename: Trongha X
authors.initials: TX
authors.lastname: Phan
authors.affiliation: Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195-7750, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Saraf
authors.affiliation: Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195-7750, USA.
authors.forename: Xuanmao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195-7750, USA dstorm@u.washington.edu.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Storm
mesh_terms: D056930:ARNTL Transcription Factors / Q000172:deficiency / Q000235:genetics; D056044:Actigraphy; D000818:Animals; D015153:Blotting, Western; D057906:Circadian Clocks / Q000502:physiology*; D004597:Electroshock; D004797:Enzyme-Linked Immunosorbent Assay; D005239:Fear / Q000502:physiology; D005528:Foot; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse