Reinnervation of dopamine-denervated striatum by substantia nigra transplants: immunohistochemical and electrophysiological correlates

Abstract

This study evaluated whether or not fetal substantia nigra tissue, grafted to striatum previously lesioned with 6-hydroxydopamine, provides functional dopaminergic reinnervation of striatum. Falck-Hillarp histochemistry and immunofluorescent staining for tyrosine hydroxylase demonstrated extensive networks of nerve fibers which extended 1-1.5 mm from the nigral grafts into striatal tissue. Multibarrel micropipettes were used to record neurons electrophysiologically and test neuronal responses to phencyclidine which was applied locally by pressure microejection. "Distal" neurons, defined as those striatal neurons more than 2.0 mm from the nigral graft, fired at an average spontaneous rate of 13.4 spikes/s and were relatively insensitive to the effects of locally applied phencyclidine. However, "proximal" neurons, defined as those neurons less than 1.0 mm from nigral grafts, fired at a significantly lower average rate of 4.9 spikes/s, and were significantly more sensitive than distal neurons to the effects of phencyclidine. These results suggest that fetal substantia nigra grafts can provide functionally significant reinnervation of striatum previously lesioned with 6-hydroxydopamine.