DOPAMINERGIC-NEURONS INTRINSIC TO THE PRIMATE STRIATUM

Intrinsic, striatal tyrosine hydroxylase-immunoreactive (TH-I) cells h ave received little consideration. In this study we have characterized these neurons and their regulatory response to nigrostriatal dopamine rgic deafferentation. TH-i cells were observed in the striatum of both control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treat ed monkeys; TH-i cell counts, however, were 3.5-fold higher in the str iatum of MPTP-lesioned monkeys. To establish the dopaminergic nature o f the TH-i cells, sections were double-labeled with antibodies to dopa mine transporter (DAT). Immunofluorescence studies demonstrated that n early all TH-i cells were double-labeled with DAT, suggesting that the y contain the machinery to be functional dopaminergic neurons. Two typ es of TH-i cells were identified in the striatum: small, aspiny, bipol ar cells with varicose dendrites and larger spiny, multipolar cells. T he aspiny cells, which were more prevalent, corresponded morphological ly to the GABAergic interneurons of the striatum. Double-label immunof luorescence studies using antibodies to TH and glutamate decarboxylase (GAD(67)), the synthetic enzyme for GABA, showed that 99% of the TH-i cells were GAD(67)-positive. Very few (<1%) of the TH-i cells, howeve r, were immunoreactive for the calcium-binding proteins calbindin and parvalbumin. In summary, these results demonstrate that the dopaminerg ic cell population of the striatum responds to dopamine denervation by increasing in number, apparently to compensate for loss of extrinsic dopaminergic innervation. Moreover, this population of cells correspon ds largely with the intrinsic GABAergic cells of the striatum. This st udy also suggests that the adult primate striatum does retain some int rinsic capacity to compensate for dopaminergic cell loss.