Serotonin Reinnervation of the Suprachiasmatic Nucleus by Intrahypothalamic Fetal Raphe Transplants, with Special Reference to Possible Influences of the Target.

Survival and development of fetal serotonin (5-HT) neurons grafted to various brain areas in adult mammals have been suggested to be under host influences. The aim of this study was to determine whether the suprachiasmatic nucleus of the hypothalamus (SCN), a region receiving a 5-HT input which is one of the densest and the most heavily synaptic in the brain, can actually support the development of transplanted 5-HT neurons. The time course and extent of 5-HT reinnervation were therefore investigated with 5-HT immunocytochemistry in adult rats subjected to intraventricular injection of 5,7-dihydroxytryptamine and subsequent grafting of fetal cell suspension of mesencephalic raphe neurons. The ultrastructural features of the newly formed 5-HT terminal plexa were also examined. Serotonin reinnervation of the SCN remained partial up to 4 months post-transplantation, with no apparent predilection of the reinnervating fibres for any particular portion of the nucleus, thus differing from the normal 5-HT innervation of the SCN both quantitatively and qualitatively. This was in sharp contrast to the 5-HT hyperinnervation observed in neighbouring areas such as the supraoptic nucleus, a structure normally provided with only few 5-HT fibres, and the ventral wall of the third ventricle. The graft-derived 5-HT axons, however, displayed ultrastructural features that did not appear different from those of their normal counterparts; in particular they re-established defined synaptic contacts with the host population. These results may indicate that the mature SCN specifically lacks a trophic factor necessary for the ingrowth of graft-derived 5-HT fibres, or that it represents an inhibitory environment for such an ingrowth. The limited ability of regrowing 5-HT axons to restore a normal density of 5-HT innervation could also be related to the fact that these neurons normally establish a relatively high number of synaptic contacts in the target region.