Dual-Color Single-Cell Imaging of the Suprachiasmatic Nucleus Reveals a Circadian Role in Network Synchrony.

The suprachiasmatic nucleus (SCN) acts as a master pacemaker driving circadian behavior and physiology. Although the SCN is small, it is composed of many cell types, making it difficult to study the roles of particular cells. Here we develop bioluminescent circadian reporter mice that are Cre dependent, allowing the circadian properties of genetically defined populations of cells to be studied in real time. Using a Color-Switch PER2::LUCIFERASE reporter that switches from red PER2::LUCIFERASE to green PER2::LUCIFERASE upon Cre recombination, we assess circadian rhythms in two of the major classes of peptidergic neurons in the SCN: AVP (arginine vasopressin) and VIP (vasoactive intestinal polypeptide). Surprisingly, we find that circadian function in AVP neurons, not VIP neurons, is essential for autonomous network synchrony of the SCN and stability of circadian rhythmicity. • Color-Switch PER2::iLuc is a novel, Cre-inducible mouse reporter for circadian rhythms • Dual-color imaging acquires and unmixes concurrent signals from distinct cell types • SCN AVP and VIP neurons have different functions in network synchrony and stability • Bmal1 has an essential function in AVP neurons for network synchrony in the SCN Shan et al. generate a Cre-inducible mouse reporter with green and red luciferases fused to PER2, enabling cell-specific circadian measurements with a dual-color imaging device. Using genetically directed bioluminescence from AVP or VIP neurons in the SCN circadian pacemaker, they unravel distinct functions of the circadian clock in these neuronal subtypes. [ABSTRACT FROM AUTHOR]