These insights may ultimately have therapeutic relevance for individuals with sleep disturbances caused by jet lag, shift work or certain sleep disorders.Ĭircadian clocks generate ∼24 hr rhythms in behavior and physiology which allow an organism to anticipate and adjust to environmental changes accompanying the earth's day/night cycle. have underlined the importance of cell-to-cell communication in these processes. Instead, it is because the loss of Lhx1-a transcription factor that controls the expression of many other genes-means that the SCN cells do not produce the proteins they need to synchronize their outputs.Īs well as identifying a key gene involved in the generation and maintenance of circadian rhythms, Hatori et al. This is not because their SCN cells fail to generate circadian rhythms. However, mice that lose Lhx1 during embryonic development survive, although they struggle to maintain circadian rhythms when kept in complete darkness. Mice with a complete absence of Lhx1 die in the womb. But one gene in particular, known as Lhx1, stood out because it was strongly suppressed by light. When mice living in 24-hr darkness were exposed to an hour of light in the early evening, they showed changes in the levels of proteins associated with many SCN genes. have identified the master regulator that controls this cross-talk. Cross-talk between these cells results in the production of a single circadian rhythm. However, each cell within the SCN also contains its own clock, and can generate rhythmic activity independently of its neighbors. The internal circadian rhythm is generated by a structure deep within the brain called the suprachiasmatic nucleus (SCN), which is essentially the ‘master clock’ of the brain. In most individuals, this internal ‘circadian rhythm’ repeats with a period of just over 24 hr, and exposure to light brings it into line with the 24-hr clock. Nevertheless, if a person is made to live in constant darkness as part of an experiment, they still continue to experience daily changes in their alertness levels. Therefore, by regulating expression of genes mediating intercellular communication, Lhx1 imparts synchrony among SCN neurons and ensures consolidated rhythms of activity and rest that is resistant to photic noise.Īs anyone who has experienced jet lag can testify, our sleeping pattern is normally synchronized with the local day–night cycle. Ex vivo recordings of the SCN from these mice showed rapid desynchronization of unit oscillators. Consequently, the mice rapidly phase shift under a jet lag paradigm and their behavior rhythms gradually deteriorate under constant condition. Mice lacking Lhx1 in the SCN have intact circadian oscillators, but reduced levels of coupling factors. A phase-shifting light pulse causes acute reduction in Lhx1 expression and of its target genes that participate in SCN coupling.
Here, we identified Lhx1 as a regulator of SCN coupling. However, factors that specify this characteristic feature of the SCN are unknown. 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.
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