THE AGE OF STRIATUM DETERMINES THE PATTERN AND EXTENT OF DOPAMINERGICINNERVATION - A NIGROSTRIATAL DOUBLE GRAFT STUDY

In animal models of Parkinson's disease, transplanted fetal mesencepha lic dopaminergic neurons can innervate the dopamine-depleted host brai n, but it is unclear why large portions of the host striatum are left uninnervated, During normal development, the dopaminergic innervation first occurs in the form of a dense patchy pattern in the striatum, fo llowed by a widespread nerve fiber network, Using intraocular double g rafts we have investigated dopaminergic growth patterns initiated when ventral mesencephalic grafts innervate striatal targets, The fetal la teral ganglionic eminence was implanted into the anterior eye chamber, After maturation in oculo, fetal ventral mesencephalon was implanted and placed in contact with the first graft, In other animals the two p ieces of tissue were implanted simultaneously, Tyrosine hydroxylase (T H) immunohistochemistry revealed a pattern of dense TH-positive patche s throughout the total volume of the striatal grafts in simultaneously transplanted cografts, while a widespread, less dense, pattern was fo und when mature striatal transplants were innervated by fetal dopamine rgic grafts, To investigate which type or types of growth patterns tha t developed after grafting to striatum in situ of an adult host, fetal ventral mesencephalic tissue was implanted into the lateral ventricle adjacent to the dopamine-lesioned striatum, After maturation of the m esencephalic graft, the fetal lateral ganglionic eminence was implante d into the reinnervated part of the host striatum, TH immunohistochemi stry revealed a few nerve fibers within the striatal graft and the gro wth pattern was of the widespread type, In conclusion, grafted dopamin ergic neurons preferably innervate mature striatum with a widespread s parse nerve fiber network, while the innervation of the immature stria tum occurs in the form of dense patches, Furthermore, when the patchy pattern is formed, the total volume of the striatal target is innervat ed while growth of the widespread type terminates prior to reaching di stal striatal parts, Thus, the growth pattern seems essential to the f inal volume that is innervated, Once the widespread growth pattern is initiated, the presence of immature striatum does not change the dopam inergic growth pattern. (C) 1997 Elsevier Science Inc.