rapid changes in the lightdark cycle disrupt memory of conditioned fear in mice在lightdark周期的快速变化破坏老鼠的条件性恐惧记忆.pdfVIP

Rapid Changes in the Light/Dark Cycle Disrupt Memory of Conditioned Fear in Mice 1 1 1 1 2 Dawn H. Loh , Juliana Navarro , Arkady Hagopian , Louisa M. Wang , Tom Deboer , Christopher S. Colwell1* 1 Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America, 2 Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands Abstract Background: Circadian rhythms govern many aspects of physiology and behavior including cognitive processes. Com- ponents of neural circuits involved in learning and memory, e.g., the amygdala and the hippocampus, exhibit circadian rhythms in gene expression and signaling pathways. The functional significance of these rhythms is still not understood. In the present study, we sought to determine the impact of transiently disrupting the circadian system by shifting the light/ dark (LD) cycle. Such ‘‘jet lag’’ treatments alter daily rhythms of gene expression that underlie circadian oscillations as well as disrupt the synchrony between the multiple oscillators found within the body. Methodology/Principal Findings: We subjected adult male C57Bl/6 mice to a contextual fear conditioning protocol either before or after acute phase shifts of the LD cycle. As part of this study, we examined the impact of phase advances and phase delays, and the effects of different magnitudes of phase shifts. Under all conditions tested, we found that recall of fear conditioned behavior was specifically affected by the jet lag. We found that phase shifts potentiated the stress-evoked corticosterone response without a