Neurotransplantation of the Biological Clock in Mammals, Importance and Perspectives

The tool of neurotransplantation has been successfully introduced in the chronobiology of mammals. Grafting of the foetal suprachiasmatic nucleus (SCN) in the IIIrd ventricle of the brain of SCN-lesioned arhythmic rodents restored free-running circadian activity patterns. This ultimately proves the SCN to be the central circadian pacemaker system. However, recovery is not seen in all animals with a surviving SCN implant and the rhythm is usually not as robust as seen for the intact system. Moreover, the grafted foetal SCN has a partially deviant development, whereas the structure-function relationship after restoration of circadian rhythm was reported to differ in the various studies. This has led to two possible mechanisms of graft action: the one a circadian humoral signal diffusing into the SCN-lesioned host brain, and the other a neuritic afferent outgrowth into the brain. There is, moreover, doubt about the integration of the 'new' SCN in terms of afferent input. Given the fact that the in situ SCN has an extensive efferent and afferent system in the intact brain, the SCN grafting experiments seem to indicate that only limited aspects of the SCN can drive circadian physiological rhythms. However, on the basis of current knowledge on grafting results the present paper recommends performing more sophisticated SCN grafting experiments to contribute to the knowledge on the SCN clock system.