Physiological, pharmacological and molecular aspects of mammalian biological clocks

Abstract

Circadian rhythm is an endogenous rhythm that persists in constant conditions with a period of nearly but not identical to 24 hr. Under natural conditions, the circadian clock is precisely entrained to the daily (24 hr) cycle, because environmental stimulus (especially light) induces a phase shift of the clock. In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus has been shown to be the primary pacemaker that drives daily rhythms of behavioral and physiological activity. Photic information is conveyed from the retina to the SCN directly by the retinohypothalamic tract (RHT) and indirectly by the geniculo-hypothalamic tract (GHT). The transmitter of the RHT is glutamate, while the GHT is GABA and neuropeptide Y. Serotonergic innervation from the median raphe and melatonin from the pineal body are likely to provide non-photic information to the SCN. Single gene mutations that dramatically alter circadian phenotype were found in the hamster (tau) and mouse (clock). Moreover, the homologous genes of the Drosophila clock gene, per, were found in mammals and the homologue of the mammalian clock was found in Drosophila. These data suggest that the some constitutes of the biological clock may be conserved between Drosophila and mammals, and a transcription-translation feedback loop involving some clock gene products may be a oscillator itself.