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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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