INTRASTRIATAL MESENCEPHALIC GRAFTS AFFECT NEURONAL-ACTIVITY IN BASAL GANGLIA NUCLEI AND THEIR TARGET STRUCTURES IN A RAT MODEL OF PARKINSONS-DISEASE

Nigrostriatal dopamine (DA) lesions lead to changes of neuronal activi ty in basal ganglia nuclei such as the globus pallidus (GP, the rodent homolog of lateral globus pallidus), entopeduncular nucleus (EP, the rodent homolog of medial globus pallidus), substantia nigra pars retic ulata (SNR), and subthalamic nucleus (STN). We investigated in rats wh ether embryonic mesencephalic DA neurons grafted in the striatum may a ffect the lesion-induced alterations of neuronal activity in these str uctures. Regional neuronal activity was determined by use of quantitat ive cytochrome oxidase histochemistry. It was also examined in lesione d rats whether the grafts may regulate the expression of c-Fos after s ystemic administration of apomorphine in the basal ganglia nuclei as w ell as their target structures, including the ventromedial thalamic nu cleus (VM), superior colliculus (SC), and pedunculopontine nucleus (PP N). Lesioned rats exhibited an increased activity of CO in the GP, EP, SNR, and STN ipsilateral to the lesion. Intrastriatal nigral grafts r eversed the increases in the CO activity in the EP and SNR, whereas th e grafts failed to affect the enzyme activity in the GP or STN. Apomor phine induced an increased expression of c-Fos in the GP, STN, VM, SC, and PPN on the lesioned side. The enhanced expression of this protein in all the structures except for the STN was attenuated by nigral gra fts. The present results indicate that intrastriatal DA neuron grafts can normalize the lesion-induced changes of neuronal activity in the o utput nuclei of the basal ganglia as well as their target structures.