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

Curr Biol. 2012 Oct 23;22(20):1871-80. doi: 10.1016/j.cub.2012.07.070. Epub 2012 Aug 30.


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(v)s) in response to altered electrical activity, including a large set of circadian genes. Hyperexciting LN(v)s 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 per(0) mutant LN(v)s but not in cyc(0) mutant LN(v)s, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 2 / physiology*
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Behavior, Animal
  • Circadian Clocks / physiology*
  • Circadian Rhythm* / genetics
  • Circadian Rhythm* / physiology
  • Cyclic AMP Response Element-Binding Protein / physiology
  • Drosophila / genetics
  • Drosophila / physiology*
  • Drosophila Proteins / physiology*
  • Gene Expression Regulation
  • Genes, Insect
  • Neurons / physiology*
  • Oligonucleotide Array Sequence Analysis
  • Sodium Channels / genetics
  • Sodium Channels / metabolism
  • Transcription, Genetic
  • Transcriptional Activation
  • Transcriptome*


  • ATF-2 protein, Drosophila
  • Activating Transcription Factor 2
  • Bacterial Proteins
  • Cyclic AMP Response Element-Binding Protein
  • Drosophila Proteins
  • NaChBac protein, bacteria
  • Sodium Channels