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Circadian modulation of cognitive function

Christopher S. Colwell
Department of Psychiatry , University of California - Los Angeles , USA

The genes responsible for the generation of circadian oscillations are expressed in a variety of brain regions not typically associated with circadian timing. The functions of this clock gene expression are just beginning to be examined, and we sought to explore the role of the mPer2 gene in hippocampal physiology and learned behavior. Using a variety of techniques including immunocytochemistry, Western Blots, and in situ hybridization, we found that mPER2 is highly expressed in hippocampal pyramidal cells. The levels of both protein and message were found to vary with a circadian rhythm. Optical imaging techniques were used to demonstrate that the rhythm in mPer2 expression is autonomous and present even in isolated hippocampal slices maintained in culture. Physiologically, mPer2-deficient mice exhibit ab normal long-term potentiation evoked by a strong stimulation protocol but do not exhibit deficits in baseline excitatory synaptic transmission. The underlying mechanism is suggested by the finding that levels of p-CREB, but not p-ERK, are reduced in hippocampal tissue from the mPer2-deficient mice. Finally, mPer2-deficient mice exhibit deficits in recall, but not acquisition, of trace fear conditioning. Together, these results provide clear evidence that the clock gene mPer2 plays a critical role in hippocampal physiology and recall of learned behavior in mammals.