Trends in Neurosciences
Volume 25, Issue 12, 1 December 2002, Pages 632-637
Journal home page for Trends in Neurosciences

Review
Time after time: inputs to and outputs from the mammalian circadian oscillators

https://doi.org/10.1016/S0166-2236(02)02274-9Get rights and content

Abstract

Oscillating levels of clock gene transcripts in the suprachiasmatic nucleus (SCN) are essential components of the mammalian circadian pacemaker. Their synchronization with daily light cycles involves neural connections from light-sensitive photoreceptor-containing retinal ganglion cells. This clock orchestrates rhythmic expression for ∼10% of the SCN gene transcripts, of which only 10% are also rhythmically expressed in other tissues. Many of the transcripts expressed rhythmically only in the SCN are involved in neurosecretion, and their secreted products could mediate SCN control over physiological rhythms by coordinating rhythmicity in other nuclei within the brain. The coordination of clock gene transcript oscillations in peripheral tissues could be controlled directly by specific signals or indirectly by rhythmic behavior such as feeding.

Section snippets

The same but different – the basic clockwork in the SCN and peripheral tissues

The components of the mammalian circadian oscillator have been studied primarily using mice carrying mutations in one or more of the clock genes. The components can be assembled into a basic wiring diagram (Fig. 1a) that involves a complex transcriptional feedback circuit of three period genes (per1, per2 and per3), two cryptochrome genes (cry1 and cry2), a clock gene (clk) and the gene encoding brain–muscle Arnt-like protein 1 (bmal1) 1., 4., 6., 7.. Levels of all the transcripts (except those

Seeing the light – identifying the photoreceptor for light input to the clock

The identity of the photopigment involved in light signaling to the mammalian circadian system has long been a mystery [36]. Cryptochromes, which have been firmly implicated as circadian photopigments in Drosophila [37] and zebrafish [38], do not seem to be essential in mammals [39]. Another interesting candidate, melanopsin, was found to be expressed specifically in the ganglion cell layer of the retina 40., 41.. This appeared important as a number of previous studies had localized the site of

Getting the word out – synchronizing oscillations in the periphery

The role of the SCN as a master timer in the circadian system implies that timing cues are continually transmitted to the rest of the body. At least part of this timing information is transmitted to other areas of the brain via physical connections [58]. One recent study has traced an indirect link from the SCN through the dorsomedial hypothalamic nucleus to the noradrenergic nucleus locus coeruleus, which is involved in regulating arousal state [59]. The neurons of the SCN have a higher

They've got rhythm – circadian gene expression in peripheral tissues

Independently of how timing signals arrive, to have any functional relevance the cells within various peripheral tissues must be able to do different things at different times of day. Several peripheral tissues have now been shown to regulate gene expression on a daily basis. Transcript profiling in serum-shocked synchronized fibroblasts 74., 75., heart [76], liver 67., 76., 77., 78., kidney [79] and the SCN itself [67] have all been reported. Several global conclusions can be drawn from this

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