Abstract
Summary Circadian clocks regulate membrane excitability in master pacemaker neurons to control daily rhythms of sleep and wake. Here, we find that two distinctly timed electrical drives collaborate to impose rhythmicity on Drosophila clock neurons. In the morning, a voltage-independent sodium conductance via the NA/NALCN ion channel depolarizes these neurons. This current is driven by the rhythmic expression of NCA localization factor-1, linking the molecular clock to ion channel function. In the evening, basal potassium currents peak to silence clock neurons. Remarkably, daily antiphase cycles of sodium and potassium currents also drive mouse clock neuron rhythms. Thus, we reveal an evolutionarily ancient strategy for the neural mechanisms that govern daily sleep and wake.
| Original language | English (US) |
|---|---|
| Article number | 8351 |
| Pages (from-to) | 836-848 |
| Number of pages | 13 |
| Journal | Cell |
| Volume | 162 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 17 2015 |
Funding
We thank B. White and H-S. Li for communicating results prior to publication; M. Vitaterna, K. Shimomura, A. Para, E. Zaharieva, D. Wokosin, C. Olker, and Jordan I. Robson for technical assistance; J. Gu, R. Scott, and B. White for the cloning and generation of UAS-NA HA flies; Dr. Jean Richa (Transgenic and Chimera Mouse Facility at the University of Pennsylvania) for ES cell injection; and M. Gallio for reagents and comments on a draft of the manuscript. We also thank Bloomington Drosophila stock center, the National Institute of Genetics (NIG), Vienna Drosophila RNAi center (VDRC) for reagents, and the TRiP at Harvard Medical School (NIH/NIGMS R01-GM084947) for providing transgenic RNAi fly stocks. This work was supported by National Institutes of Health (NIH) grants R01NS052903 and R01MH092273 (to R.A.), NS055293 and NS074257 (to D.R.), R00GM080107 (to B.C.L.), and National Science Foundation (NSF) Division of Mathematical Science grant (DMS1412877 to C.O.D.). This effort was in part sponsored by the Defense Advanced Research Projects Agency (DARPA) (D12AP00023, to R.A.); the content of the information does not necessarily reflect the position or the policy of the government, and no official endorsement should be inferred. This work was also supported by the Northwestern University Flow Cytometry Facility, by a Cancer Center Support Grant (NCI CA060553).The two-photon microscope was supported by NINDS (NS054850). A.L.H. is a trainee of the NIH Medical Scientist Training program at the University of Chicago (NIGMS T32GM07281). This work made use of the Open Science Data Cloud (OSDC), which is an Open Cloud Consortium (OCC)-sponsored project. This work was supported, in part, by grants from Gordon and Betty Moore Foundation, the NSF, and major contributions from OCC members like the University of Chicago. Our work is in memory of Howard Nash, who re-discovered narrow abdomen and inspired our pursuit of studies of this channel.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology