Connectivities of the striatal grafts in adult rat brain: a rich afference and scant striatonigral efference

Abstract

Previous reports from this laboratory have indicated that fetal rat striatal grafts have the major types of neuronal and glial components known to be involved in Huntington's chorea. In this study a number of major afferent and efferent innervations seen in normal striatum were examined in the striatal grafts and were compared with embryonic striatal afferents. First, using immunocytochemistry and histochemistry, the host serotonergic (5-HT), dopaminergic (DA, stained with anti-tyrosine hydroxylase (TH) antiserum), and acetylcholinesterase (AChE) fibers exhibited vigorous growth into the grafts implanted in neostriatum, lateral ventrice, globus pallidus or substantia nigra within a period of 6 and 10 weeks. Individual characteristic terminal patterns formed in striatal grafts: 5-HT fibers were diffused; TH fibers became heavily packed, and AChE fibers were patchy. This peculiar patternization of 5-Ht and TH growth into striatal graft appeared to be a recapitulation of the normal 5-HT and TH growth into striatum in the embryonic stage. However, a significantly show (6 week) onset of adult 5-HT and TH ingrowth into the fetal graft was noted, as compared with that of normal embryonic development (5–6 days from the appearance of 5-HT and TH neurons). With the anterograde-transport marker Phaseolus vulgaris agglutinin leuca method, host cortical neurons also projected to the graft, but in limited numbers. Finally, with the retrograde-transport marker (horseradish peroxidase method, the grafts implanted in neostriatum were found incapable of sending fibers to a major, distal target, substantia nigra. In a current evaluation of striatal transplants, it is shown that major input to the graft can be achieved over time, but output to the distal nigra seems an unrealistic expectation. These data suggest that: (1) the fetal brain tissue was found to be a strong stimulant for sprouting or regeneration of adult nerve fibers; (2) a number of functional recoveries reported on the tested behavior paradigm in this grafting model could be due to the survival of striatal graft and the establishment of input circuitries; further, (3) the data illustrate the necessity of seeking a bridge from the striatal transplant to the host nigra. If a proper functional recovery in Huntington's chorea requires complete striatonigral circuitry, then such a bridge is worthy of a major investigation.