Circadian lessons from peripheral clocks: is the time of the mammalian pacemaker up?

T he pineal gland of house sparrows was one of the first biological clocks believed to act as a circadian pacemaker. This view came from brilliant experimental studies by Menaker and coworkers (1, 2) demonstrating that removal of the pineal gland caused arrhythmic behavior and transplantation of pineal glands into pinealectomized arrhythmic birds restored locomotor rhythms. Takahashi and Menaker (3) extended this view by providing evidence for the multioscillatory nature of the house sparrow circadian system, demonstrating the presence of hypothalamic components and the necessity of coupling of oscillators to maintain rhythmicity. The interesting suggestion of two oscillators remaining in the hypothalamus of pinealectomized sparrows found experimental evidence 20 years later when rhythmic and pinealindependent clock gene expression was found in two cell groups of the house sparrow hypothalamus: the suprachiasmatic nucleus (SCN) and the lateral hypothalamic nucleus (4–6).