Vasoactive intestinal peptide efferent projections of the suprachiasmatic nucleus in anterior hypothalamic transplants: correlation with functional restoration of circadian behavior.

Circadian rhythmicity can be restored by transplantation of fetal anterior hypothalamic (AH) tissue containing the suprachiasmatic nucleus (SCN) into hosts rendered arrhythmic by SCN ablation. However, the nature of the SCN effector pathways mediating functional recovery has remained elusive. To examine implant-derived SCN innervation of the host, AH homografts (hamster-to-hamster) and heterografts (mouse- or rat-to-hamster) were employed and the distribution of vasoactive intestinal peptide (VIP) within the SCN terminal fields was evaluated. A comparison was made between cases where circadian locomotor activity was restored and cases where circadian rhythmicity remained disrupted following AH transplantation. A dense aggregation of VIP neurons and processes was identified in each transplant that restored behavioral rhythmicity in the host. In these cases, SCN-derived VIP fibers were integrated with the host brain and could be identified in host terminal fields typically innervated by SCN-VIP fibers. A correlation was noted between VIP innervation of the host paraventricular thalamic nucleus (PVT) and restoration of circadian rhythmicity. Neither qualitative nor quantitative differences in transplant VIP projections were noted between AH homografts and heterografts. These results demonstrate that SCN VIP neurons in AH transplants send an appropriately restricted set of efferent projections to the host brain and suggest that SCN efferent projections to the PVT may participate in mediating the functional recovery of circadian locomotor activity.