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Previous Article | Next Article
The Journal of Neuroscience, April 15, 2001, 21(8):2610-2621
The Homeostatic Regulation of Sleep Need Is under Genetic Control
Paul Franken1, 2, Didier Chollet1, and Mehdi Tafti1 1 Biochemistry and Neurophysiology Unit, Department of Psychiatry, University of Geneva, Chêne-Bourg, Switzerland, and 2 Department of Biological Sciences, Stanford University, Stanford, California 94305-5020
Delta power, a measure of EEG activity in the 1-4 Hz range, in slow-wave sleep (SWS) is in a quantitative and predictive relationship with prior wakefulness. Thus, sleep loss evokes a proportional increase in delta power, and excess sleep a decrease. Therefore, delta power is thought to reflect SWS need and its underlying homeostatically regulated recovery process. The neurophysiological substrate of this process is unknown and forward genetics might help elucidate the nature of what is depleted during wakefulness and recovered during SWS. We applied a mathematical method that quantifies the relationship between the sleep-wake distribution and delta power to sleep data of six inbred mouse strains. The results demonstrated that the rate at which SWS need accumulated varied greatly with genotype. This conclusion was confirmed in a "dose-response" study of sleep loss and changes in delta power; delta power strongly depended on both the duration of prior wakefulness and genotype. We followed the segregation of the rebound of delta power after sleep deprivation in 25 BXD recombinant inbred strains by quantitative trait loci (QTL) analysis. One "significant" QTL was identified on chromosome 13 that accounted for 49% of the genetic variance in this trait. Interestingly, the rate at which SWS need decreases did not vary with genotype in any of the 31 inbred strains studied. These results demonstrate, for the first time, that the increase of SWS need is under a strong genetic control, and they provide a basis for identifying genes underlying SWS homeostasis.
Key words: EEG delta power; slow-wave activity; sleep deprivation; homeostatic regulation of non-REM sleep; simulation of Process S; BXD recombinant-inbred mouse strains; QTL; Dps1; Dps2; Dps3; forward genetics
Copyright © 2001 Society for Neuroscience 0270-6474/01/2182610-12$05.00/0
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