Article abstract
Nature Neuroscience 11, 354 - 359 (2008)
Published online: 27 January 2008 | doi:10.1038/nn2046
Modulation of GABAA receptor desensitization uncouples sleep onset and maintenance in Drosophila
Jose Agosto1,2,3, James C Choi2,3,5, Katherine M Parisky2,3, Geoffrey Stilwell4, Michael Rosbash1,2,3 & Leslie C Griffith2,3
Abstract
Many lines of evidence indicate that GABA and GABAA receptors make important contributions to human sleep regulation. Pharmacological manipulation of these receptors has differential effects on sleep onset and sleep maintenance insomnia. Here we show that sleep is regulated by GABA in Drosophila and that a mutant GABAA receptor, RdlA302S, specifically decreases sleep latency. The drug carbamazepine (CBZ) has the opposite effect on sleep; it increases sleep latency as well as decreasing sleep. Behavioral and physiological experiments indicated that RdlA302S mutant flies are resistant to the effects of CBZ on sleep latency and that mutant RDLA302S channels are resistant to the effects of CBZ on desensitization, respectively. These results suggest that this biophysical property of the channel, specifically channel desensitization, underlies the regulation of sleep latency in flies. These experiments uncouple the regulation of sleep latency from that of sleep duration and suggest that the kinetics of GABAA receptor signaling dictate sleep latency.
- Howard Hughes Medical Institute, Brandeis University, 415 South St., Waltham, Massachusetts 02454-9110, USA
- Department of Biology, Brandeis University, 415 South St., Waltham, Massachusetts 02454-9110, USA
- National Center for Behavioral Genomics, Brandeis University, 415 South St., Waltham, Massachusetts 02454-9110, USA.
- Cambria Biosciences, Woburn, Massachusetts 01801, USA.
- Present address: Department of Neurology, Neurobiology Program, Children's Hospital, Boston, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Correspondence to: Leslie C Griffith2,3 e-mail: griffith@brandeis.edu
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