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The Journal of Neuroscience, January 15, 2000, 20(2):617-625

The Transcription Factor DBP Affects Circadian Sleep Consolidation and Rhythmic EEG Activity

Paul Franken1, Luis Lopez-Molina2, Lysiane Marcacci2, Ueli Schibler2, and Mehdi Tafti1

1 Biochemistry and Neurophysiology Unit, Department of Psychiatry, University of Geneva, CH-1225 Chêne-Bourg, Switzerland, and 2 Department of Molecular Biology, Sciences II, University of Geneva, CH-1211 Geneva, Switzerland

Albumin D-binding protein (DBP) is a PAR leucine zipper transcription factor that is expressed according to a robust circadian rhythm in the suprachiasmatic nuclei, harboring the circadian master clock, and in most peripheral tissues. Mice lacking DBP display a shorter circadian period in locomotor activity and are less active. Thus, although DBP is not essential for circadian rhythm generation, it does modulate important clock outputs. We studied the role of DBP in the circadian and homeostatic aspects of sleep regulation by comparing DBP deficient mice (dbp-/-) with their isogenic controls (dbp+/+) under light-dark (LD) and constant-dark (DD) baseline conditions, as well as after sleep loss. Whereas total sleep duration was similar in both genotypes, the amplitude of the circadian modulation of sleep time, as well as the consolidation of sleep episodes, was reduced in dbp-/- under both LD and DD conditions. Quantitative EEG analysis demonstrated a marked reduction in the amplitude of the sleep-wake-dependent changes in slow-wave sleep delta power and an increase in hippocampal theta peak frequency in dbp-/- mice. The sleep deprivation-induced compensatory rebound of EEG delta power was similar in both genotypes. In contrast, the rebound in paradoxical sleep was significant in dbp+/+ mice only. It is concluded that the transcriptional regulatory protein DBP modulates circadian and homeostatic aspects of sleep regulation.

Key words: sleep homeostasis; non-REM sleep intensity; knock-out mice; clock-genes; EEG and circadian oscillations; simulation

Copyright © 2000 Society for Neuroscience  0270-6474/00/202617-09$05.00/0


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