Ultrastructural analysis of graft-to-host connections, with special reference to dopamine-neuropeptide Y interactions in the rat striatum, after transplantation of fetal mesencephalon cells.

Abstract

In a previous study we demonstrated that grafted dopamine (DA) neurons are able to induce an early and widespread normalization of DA-neuropeptide Y (NPY) interactions in the host striatum previously deprived of its DA input. Since similar recoveries were found to occur in striatal areas densely or poorly reinnervated by the graft, the question was raised as to what mechanisms (synaptic or volumic release) were involved in these functional effects. Ultrastructural analysis of graft-to-host relationships was performed using single--and double--immunolabelling techniques to detect neurons containing tyrosine hydroxylase (TH) and NPY, with a view to analysing the early establishment of synaptic connectivity in various areas of the host striatum. Within 1 month of the grafting, TH-immunoreactive (TH-IR) neurons showed most of the normal intrinsic morphological features characteristic of adult rat neurons and were found to have established direct relationships with various striatal neuronal populations. TH-NPY relationships were observed only in the area most densely reinnervated by the graft, and their relative frequency was found to be roughly the same as that determined in the intact striatum. Three months after the grafting, this percentage decreased, probably owing to the further elongation in TH-IR axons resulting in a wider distribution of the TH-NPY associations over the host striatum. In the zones distal from the graft, the reinnervation was far from complete and the few TH-IR fibres projected only to some unlabelled elements, mainly of the spiny type, which have been shown to interact normally with both DA afferents and NPY cells and therefore may relay the DA action over the whole striatum on the NPY population. It can be concluded from these data that the rapid and extensive functional normalization of the TH-NPY interactions previously found to occur in the entire striatum may depend on the restoration of direct and indirect synaptic relationships. A diffuse action of DA through non-synaptic mechanisms may also account for the fact that the amine has access to broader striatal populations than to those presumably reached by DA fibres arising from the graft.