Recent experiments indicate that intercellular signaling is important in generating accurate circadian rhythms. In Drosophila, the small ventral lateral neurons (s-LNvs) seem to be the dominant pacemaker neurons since they set the pace of the majority of other clock neurons in the brain, at least in constant darkness. Here I describe evidence that two independent G-protein signaling pathways in LNvs are required for 24hr rhythms. Reducing signaling in LNvs via the G-alpha subunit Gs, which signals via cAMP, or via the G-alpha subunit Go, which I show signals via Phospholipase 21c, lengthens the period of behavioral rhythms. In contrast, constitutively activating Gs or Go signaling in LNvs causes most flies to become arrhythmic. Using dissociated LNvs in culture, I found that Go signaling is required for the inhibitory effects of GABA on LNvs via the metabotropic GABAB-R3 receptor. Reducing GABAB-R3 expression in LNvs in vivo lengthens period. Although no clock neurons produce GABA, hyper-exciting GABAergic neurons disrupt behavioral rhythms and s-LNv molecular clocks. Therefore, I propose that s-LNvs require input signals, including GABA, to keep their molecular clocks running with a 24hr period.
|Commitee:||Desplan, Claude, Klann, Eric, Nitabach, Michael N., Tranchina, Daniel|
|School:||New York University|
|School Location:||United States -- New York|
|Source:||DAI-B 71/07, Dissertation Abstracts International|
|Keywords:||Circadian rhythms, G-proteins, GABA, Lateral neurons, Pacemaker neurons|
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