RESTORATION OF CIRCADIAN BEHAVIOR BY ANTERIOR HYPOTHALAMIC HETEROGRAFTS

The suprachiasmatic nucleus (SCN) of the anterior hypothalamus (AH) is a circadian oscillator and an important component of the mammalian circadian system. To determine whether the SCN is the dominant circadian pacemaker responsible for generating a species-typical characteristic of circadian rhythms [i.e., period length (tau)], neural transplantation was conducted using fetal AH donors of different species and SCN-lesioned (SCNx) hosts. The circadian behavior of each of the three donor species is clearly distinguishable by its species-typical tau. The extent of SCN pacemaker autonomy was assessed by noting whether the period of the restored circadian rhythm following heterograft transplantation was characteristic of the donor or the host, or whether an atypical circadian period was established. Hamsters rendered arhythmic by SCN ablation were implanted with AH tissue from fetal hamsters (E13-E14, homograft controls) or fetal mice or rats (E15-E17). The AH homografts restored circadian activity rhythms with a tau similar to that of intact hamsters, and fetal mouse AH heterografts restored circadian rhythmicity with a tau similar to that of the donor mouse strain. However, fetal rat AH tissue implanted into SCNx hamsters renewed circadian rhythmicity with a period significantly shorter than either the species-typical tau of the rat donor or the hamster host. In both the mouse and rat AH heterograft experiments, immunocytochemical analysis performed with species-specific monoclonal antibodies revealed extensive fiber outgrowth from the implant into the host hypothalamus, evident up to 7 months postimplantation. The rat implants were consistently larger, more fully vascularized and exhibited less necrosis than the implanted mouse tissue. The histological appearance of the grafts, thus, provides no explanation for the difference in efficacy of the grafts to restore species-typical behavior. However, several interpretations are considered that are consistent with the combined behavioral results observed.