A mechanism for circadian control of pacemaker neuron excitability.

Although the intracellular molecular clocks that regulate circadian (~24 h) behavioral rhythms are well understood, it remains unclear how molecular clock information is transduced into rhythmic neuronal activity that in turn drives behavioral rhythms. To identify potential clock outputs, the authors generated expression profiles from a homogeneous population of purified pacemaker neurons (LN(v)s) from wild-type and clock mutant Drosophila. They identified a group of genes with enriched expression in LN(v)s and a second group of genes rhythmically expressed in LN(v)s in a clock-dependent manner. Only 10 genes fell into both groups: 4 core clock genes, including period (per) and timeless (tim), and 6 genes previously unstudied in circadian rhythms. The authors focused on one of these 6 genes, Ir, which encodes an inward rectifier K(+) channel likely to regulate resting membrane potential, whose expression peaks around dusk. Reducing Ir expression in LN(v)s increased larval light avoidance and lengthened the period of adult locomotor rhythms, consistent with increased LN(v) excitability. In contrast, increased Ir expression made many adult flies arrhythmic and dampened PER protein oscillations. The authors propose that rhythmic Ir expression contributes to daily rhythms in LN(v) neuronal activity, which in turn feed back to regulate molecular clock oscillations.