Abstract
Sleep is regulated by a circadian clock that times sleep and wake to specific times of day and a homeostat that drives sleep as a function of prior wakefulness [1]. To analyze the role of the circadian clock, we have used the fruit fly Drosophila [2]. Flies display the core behavioral features of sleep, including relative immobility, elevated arousal thresholds, and homeostatic regulation [2, 3]. We assessed sleep-wake modulation by a core set of circadian pacemaker neurons that express the neuropeptide PDF. We find that disruption of PDF function increases sleep during the late night in light:dark and the first subjective day of constant darkness. Flies deploy genetic and neurotransmitter pathways to regulate sleep that are similar to those of their mammalian counterparts, including GABA [4]. We find that RNA interference-mediated knockdown of the GABAA receptor gene, Resistant to dieldrin (Rdl), in PDF neurons reduces sleep, consistent with a role for GABA in inhibiting PDF neuron function. Patch-clamp electrophysiology reveals GABA-activated picrotoxin-sensitive chloride currents on PDF+ neurons. In addition, RDL is detectable most strongly on the large subset of PDF+ pacemaker neurons. These results suggest that GABAergic inhibition of arousal-promoting PDF neurons is an important mode of sleep-wake regulation in vivo.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 386-390 |
| Number of pages | 5 |
| Journal | Current Biology |
| Volume | 19 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 10 2009 |
Funding
We thank Indira Raman for advice on the electrophysiology experiments and comments on the manuscript. We thank Leslie Griffith and Michael Rosbash for communicating results prior to publication. We acknowledge Anup Patel for providing the initial data supporting a role for Rdl in PDF neurons, Tim Requarth for identifying a control line for the Vienna Drosophila RNAi Center collection, and Sarah Sirajjuddin for the GAD-GAL4 synaptobrevin experiments. We would also like to thank Erin Petrik for expert technical assistance. This work was funded in part by the National Institutes of Health (NIH) R01 NS052903 and MH067870 and the Burroughs Wellcome Fund. B.Y.C. was supported by an NIH training grant in sleep research to the Center for Sleep and Circadian Biology at Northwestern University (T32HL07909) and by a National Research Service Award from the National Institute of Neurological Disorders and Stroke (F31NS062551).
Keywords
- MOLNEURO
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
- General Agricultural and Biological Sciences