TY - JOUR
T1 - Drosophila Pacemaker Neurons Require G Protein Signaling and GABAergic Inputs to Generate Twenty-Four Hour Behavioral Rhythms
AU - Dahdal, David
AU - Reeves, David C.
AU - Ruben, Marc
AU - Akabas, Myles H.
AU - Blau, Justin
N1 - Funding Information:
We thank Harold Atwood, Mike Forte, Leslie Griffith, Paul Hardin, Dierk Reiff, Gregg Roman, Julie Simpson, Andrew Tomlinson, Bloomington Stock Center, DSHB, and VDRC for flies and antibodies. We thank Chris Wegener for sharing unpublished data and Gregg Roman and Mike Nitabach for their advice and suggestions. We thank Karim Baroudy, Taniya Kaur, and Alyson Knowles for help in the initial stages of this project and Ben Collins for help with dissections. We also thank Matthieu Cavey, Ben Collins, Alex Keene, Dogukan Mizrak, Afroditi Petsakou, and Daniel Vasiliauskas for comments on the manuscript. Confocal images were obtained in the NYU Center for Genomics & Systems Biology. The investigation was largely conducted in a facility constructed with support from Research Facilities Improvement Grant Number C06 RR-15518-01 from National Center for Research Resources, National Institutes of Health (NIH). The work was supported by NIH grants NS030808 (M.A.) and GM063911 (J.B.).
PY - 2010/12/9
Y1 - 2010/12/9
N2 - Intercellular signaling is important for accurate circadian rhythms. In Drosophila, the small ventral lateral neurons (s-LNvs) are the dominant pacemaker neurons and set the pace of most other clock neurons in constant darkness. Here we show that two distinct G protein signaling pathways are required in LNvs for 24 hr rhythms. Reducing signaling in LNvs via the G alpha subunit Gs, which signals via cAMP, or via the G alpha subunit Go, which we show signals via Phospholipase 21c, lengthens the period of behavioral rhythms. In contrast, constitutive Gs or Go signaling makes most flies arrhythmic. Using dissociated LNvs in culture, we found that Go and the metabotropic GABAB-R3 receptor are required for the inhibitory effects of GABA on LNvs and that reduced GABAB-R3 expression in vivo lengthens period. Although no clock neurons produce GABA, hyperexciting GABAergic neurons disrupts behavioral rhythms and s-LNv molecular clocks. Therefore, s-LNvs require GABAergic inputs for 24 hr rhythms.
AB - Intercellular signaling is important for accurate circadian rhythms. In Drosophila, the small ventral lateral neurons (s-LNvs) are the dominant pacemaker neurons and set the pace of most other clock neurons in constant darkness. Here we show that two distinct G protein signaling pathways are required in LNvs for 24 hr rhythms. Reducing signaling in LNvs via the G alpha subunit Gs, which signals via cAMP, or via the G alpha subunit Go, which we show signals via Phospholipase 21c, lengthens the period of behavioral rhythms. In contrast, constitutive Gs or Go signaling makes most flies arrhythmic. Using dissociated LNvs in culture, we found that Go and the metabotropic GABAB-R3 receptor are required for the inhibitory effects of GABA on LNvs and that reduced GABAB-R3 expression in vivo lengthens period. Although no clock neurons produce GABA, hyperexciting GABAergic neurons disrupts behavioral rhythms and s-LNv molecular clocks. Therefore, s-LNvs require GABAergic inputs for 24 hr rhythms.
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U2 - 10.1016/j.neuron.2010.11.017
DO - 10.1016/j.neuron.2010.11.017
M3 - Article
C2 - 21145008
AN - SCOPUS:78649909983
SN - 0896-6273
VL - 68
SP - 964
EP - 977
JO - Neuron
JF - Neuron
IS - 5
ER -