Electrical activity can impose time of day on the circadian transcriptome of pacemaker neurons

Background: Circadian (∼24 hr) rhythms offer one of the best examples of how gene expression is tied to behavior. Circadian pacemaker neurons contain molecular clocks that control 24 hr rhythms in gene expression that in turn regulate electrical activity rhythms to control behavior. Results: Here we demonstrate the inverse relationship: there are broad transcriptional changes in Drosophila clock neurons (LN_vs) in response to altered electrical activity, including a large set of circadian genes. Hyperexciting LN _vs creates a morning-like expression profile for many circadian genes while hyperpolarization leads to an evening-like transcriptional state. The electrical effects robustly persist in per⁰ mutant LN_vs but not in cyc⁰ mutant LN_vs, suggesting that neuronal activity interacts with the transcriptional activators of the core circadian clock. Bioinformatic and immunocytochemical analyses suggest that CREB family transcription factors link LN_v electrical state to circadian gene expression. Conclusions: The electrical state of a clock neuron can impose time of day to its transcriptional program. We propose that this acts as an internal zeitgeber to add robustness and precision to circadian behavioral rhythms.