• Reciprocal CLK ↔ PDF loop (Mezan et al. 2016). Live transcriptional reporters in ex‑vivo brains revealed that CLK activity suppresses pdf transcription via DHR38/SR, while PDF signalling is required to maintain high‑fidelity CLK oscillations—a previously unseen feedback that marries electrical firing to the canonical transcriptional loop. 

• Network buffering of weak molecular rhythms (Weiss et al. 2014). When CLK‑driven transcription is artificially flattened by ~60–90 %, circadian behaviour remains robust only if PDF‑positive neurons keep higher amplitude than the rest of the network, cementing a hierarchical pacemaker‑syncytium model. 

• Electrical → molecular cross‑talk. Combining Mezan’s CLK‑PDF circuit with earlier work on PDF neuron firing explains how synaptic activity can instantaneously reset molecular phase, ensuring coherence after environmental shocks. 

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Take‑home Circadian timekeeping in Drosophila is not a solo oscillator but a reciprocally coupled molecular‑neuronal network. PDF neurons act as both conductors and metronomes, stabilising behavioural rhythms even when intracellular loops falter.