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 ci rcadian 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 transplantat ion was conducted using fetal AH donors of different species and SCN-l esioned (SCNx) hosts. The circadian behavior of each of the three dono r species is clearly distinguishable by its species-typical tau. The e xtent of SCN pacemaker autonomy was assessed by noting whether the per iod of the restored circadian rhythm following heterograft transplanta tion was characteristic of the donor or the host, or whether an atypic al circadian period was established. Hamsters rendered arhythmic by SC N ablation were implanted with AH tissue from fetal hamsters (E13-E14, homograft controls) or fetal mice or rats (E15-E17). The AH homograft s restored circadian activity rhythms with a tau similar to that of in tact hamsters, and fetal mouse AH heterografts restored circadian rhyt hmicity with a tau similar to that of the donor mouse strain. However, fetal rat AH tissue implanted into SCNx hamsters renewed circadian rh ythmicity with a period significantly shorter than either the species- typical tau of the rat donor or the hamster host. In both the mouse an d rat AH heterograft experiments, immunocytochemical analysis performe d 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, provid es no explanation for the difference in efficacy of the grafts to rest ore species-typical behavior. However, several interpretations are con sidered that are consistent with the combined behavioral results obser ved.