Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus.

Cryptochrome (Cry) 1 and Cry2 are regarded as critical components for circadian rhythm generation in mammals. Nevertheless, cultured suprachiasmatic nucleus (SCN) of neonatal Cry double deficient (Cry1(-/-)/Cry2(-/-)) mice exhibit circadian rhythms that damp out in several cycles. Here, by combining bioluminescence imaging of Per1-luc and PER2::LUC with multielectrode recording, we show developmental changes in SCN circadian rhythms in Cry1(-/-)/Cry2(-/-) mice. At the tissue level, circadian rhythms are found in neonatal but not in adult SCN, whereas at the cellular level, rhythms are detected in both SCN. Cellular circadian rhythms are synchronized in neonates, but not in adults, indicating a loss of rhythm synchrony in the course of development. Synchronized circadian rhythms in adult Cry1(-/-)/Cry2(-/-) SCN are restored by coculture of neonatal, but not of juvenile, SCN. These findings indicate that CRY1 and CRY2 are necessary for the development of intercellular networks that subserve coherent rhythm expression in adult SCN.