National Academy of Sciences, Proceedings of the National Academy of Sciences, 10(113), p. 2732-2737, 2016
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Significance Daily cycles of behavior adapt us to the 24-h rhythm of day and night. These rhythms are coordinated by a central clock, the suprachiasmatic nucleus (SCN), in which self-sustaining transcriptional/posttranslational feedback loops define approximately 24-h (circadian) time. Cryptochrome1 (CRY1) and CRY2 are essential clock components, but how they sustain cell-autonomous and circuit-level circadian timing in the SCN is not clear. To explore this, we developed a genetic complementation assay, using virally expressed, fluorescently tagged CRY proteins to test whether molecular pacemaking can be induced in arrhythmic Cry1/2 -deficient SCN. We demonstrate protein-specific and robust induction of molecular pacemaking, the efficacy of which depends on the circadian pattern and phase of Cry expression and functional signaling via neuropeptide (AVP) receptors.