The Journal of Neuroscience, October 1, 1998, 18(19):8032-8037
Melatonin Entrains the Restored Circadian Activity Rhythms of
Syrian Hamsters Bearing Fetal Suprachiasmatic Nucleus Grafts
Julia
Grosse and
Fred C.
Davis
Department of Biology, Northeastern University, Boston,
Massachusetts 02115
A circadian pacemaker consists of at least three essential
features: the ability to generate circadian oscillations, an output signal, and the ability to be entrained by external signals. In rodents, ablation of the suprachiasmatic nucleus (SCN) results in the
loss of circadian rhythms in activity. Rhythmicity can be restored by
transplanting fetal SCN into the brain of the lesioned animal,
demonstrating the first two of the essential pacemaker features within
the grafts. External signals, such as the light/dark cycle, have not,
however, been shown to entrain the restored rhythms. Melatonin
injections are an effective entraining stimulus in fetal and neonatal
Syrian hamsters of the same developmental ages used to provide donor
tissue for transplantation. Therefore, melatonin was used to test the
hypothesis that SCN grafts contain an entrainable pacemaker. Daily
injections of melatonin were given to SCN-lesioned hosts beginning on
the day after transplantation of fetal SCN. Two groups that received
melatonin at different times of day 12 hr apart each showed
significantly clustered phases but with average phases that differed by
8.67 hr. Thus melatonin was able to entrain the restored circadian
activity rhythms. In contrast to these initial injections, injections
given 6 weeks after transplantation were unable to entrain or phase
shift the rhythms. The results demonstrate that SCN grafts contain an
entrainable circadian pacemaker. In addition, the results also indicate
that the fetal SCN is directly sensitive to melatonin and, as with
intact hamsters, sensitivity to melatonin is lost during SCN
development.
Key words:
suprachiasmatic nucleus; graft; circadian rhythm; transplantation; pineal; melatonin
Copyright © 1998 Society for Neuroscience 0270-6474/98/18198032-06$05.00/0