THE DEVELOPING CIRCADIAN TIMING SYSTEM: FUNCTIONAL APPEARANCE OF LIGHT-DARK ENTRAINMENT

Abstract

In rats, it is not until postnatal day 4 that the retinohypothalamic tracts, which convey entraining information about lighting from the retina to the circadian clock in the suprachiasmatic nuclei (SCN) in the adult, begin to innervate the SCN. We thus examined when during development retina-mediated entrainment occurs. Circadian output was monitored in rat pups by measuring the rhythm in pineal N-acetyltransferase (NAT) activity. Timed pregnant rats were exposed to diurnal lighting throughout pregnancy. In one study, on the day of birth half the pups in each of 10 litters and all dams were blinded (bilateral enucleation); all were then exposed to a reversed lighting cycle until day 10 when they were placed in constant darkness. The population profiles of NAT activity on postnatal day 11 were clearly rhythmic for both groups; the intact pups were entrained to reversed lighting while the blind pups were still in phase with the prenatal (diurnal) lighting cycle. In another study, on the day of birth only the dams were blinded. The blind dams with their intact pups were then exposed to reversed lighting until either postnatal day 6 or 8 (6 litters for each group) when the animals were placed and thereafter kept in constant darkness. Analysis of pup NAT profiles on postnatal day 10 showed that the pups exposed to reversed lighting until day 8 were synchronized to reverse lighting while those exposed to reversed lighting until day 6 were only partially synchronized to reversed lighting. Thus, extraretinal mechanisms do not entrain the developing circadian system and retina-mediated entrainment is evident by postnatal day 6.