Quasimodo mediates daily and acute light effects on Drosophila clock neuron excitability

We have characterized a novel light-input pathway regulating Drosophila clock neuron excitability. The molecular clock drives rhythmic electrica lexcitability of clock neurons and we show that the recently discovered light input factor Quasimodo (Qsm) regulates this variation presumably via a Na⁺,K⁺, Cl^- co-transporter (NKCC) and the Shaw K⁺channel (dK_V3.1). Due to light-dependent degradation of the clock protein Timeless (Tim), constant illumination (LL) leads to a breakdown of molecular and behavioral rhythms. Both over-expression (^OX) and knock-down (^RNAi) of qsm, NKCC or Shaw led to robust LL-rhythmicity. Whole-cell recordings of the large ventral lateral neurons (l-LNv) showed that altering Qsm levels reduced the daily variation in neuronal activity: qsm^OX led to a constitutive less active, night-like state, and qsm^RNAi to a more active, day-like state. Qsm also affected daily changes in K⁺ currents and the GABAreversal potential, suggesting a role in modifying membrane currents and GABA responses in a daily fashion, potentially modulating light arousal and input to the clock. When directly challenged with blue light, wild-type l-LNvs responded with an increase in firing at night and no net-response during the day, while altering Qsm, NKKC or Shaw levels abolished these day/night differences. Finally, co-expression of Shaw^OX and NKCC^RNAi in a qsm mutant background restored LL-induced behavioral arrhythmicity and wild-type neuronal activity patterns, suggesting that the three genes operate in the same pathway. We propose that Qsm affects both daily and acute light effects in l-LNvs probably acting on Shaw and NKCC.