Lhx1 maintains synchrony among circadian oscillator neurons of the SCN

The robustness and limited plasticity of the master circadian clock in the suprachiasmatic nucleus (SCN) is attributed to strong intercellular communication among its constituent neurons. However, factors that specify this characteristic feature of the SCN are unknown. Here we identified Lhx1 as a regulator of SCN coupling. A phase-shifting light pulse causes acute reduction in Lhx1 expression and of its target genes that participate in SCN coupling. Mice lacking Lhx1 in the SCN have intact circadian oscillators, but reduced levels of coupling factors. Consequently, the mice rapidly phase shift under a jetlag paradigm and their behavior rhythms gradually deteriorate under constant conditions. Ex vivo recordings of the SCN from these mice showed rapid desynchronization of unit oscillators. Therefore, by regulating the expression of genes mediating intercellular communication, Lhx1 imparts synchrony to SCN neurons and ensures consolidated rhythms of activity and rest that are resistant to photic noise.