94080 in the globus pallidus (pallidotomy) have been tried. Pallidotomy was practiced prior to the development of The Disease L-DOPA, discarded, and recently regained acceptance Parkinson's disease is the third most common neurode- (Lang et al., 1997). The rationale behind pallidotomy is generative disorder, with a prevalence of approximately easy to understand. Since in the absence of dopaminer-1% of the population over 65. Affected individuals suffer gic inputs the globus pallidus is hyperactive, selective from debilitating deficiencies in motor functions that lesions will weaken its activity and reduce it to normal manifest in (1) rhythmic tremors at rest, (2) inability to levels. Similar rationale also led to the usage of highinitiate (akinesia) or complete (bradykinesia) routine frequency (inhibitory) electrical stimulation in the submovements, (3) muscle rigidity that leads to jerked mothalamic nucleus. The subthalamic nucleus normally tions, (4) postural instability, and (5) lack of facial expresstimulates the globus pallidus, and its inhibition helps sion. The disease is predominantly nonfamilial and does reduce globus pallidus activity (Figure 1). not show gender or racial bias. It is invariably progres-Although pallidotomy and electrical stimulation show sive and 5-10 years after onset the worst patients are promise in reducing akinesia and bradykinesia-espeleft bedridden and die of infections or secondary complicially akinesia that is induced by L-DOPA in advanced cations.Parkinson's patients-they are not consistently effec-The clinical symptoms are caused by a selective loss tive in reducing tremors. In addition, many symptoms of pigmented dopamine-producing neurons from the recur after only a few years. Thus, a third therapeutic substantia nigra in the midbrain and a consequent deapproach was called for-transplantation (Yurek and crease in dopamine at the innervation targets of these Sladek, 1990). The rationale behind transplantation for neurons, which include the striatum, cortex, and nucleus Parkinson's disease is again straightforward: the idea accumbens.is to replace lost dopaminergic neurons with a graft of The cause of cell death in Parkinson's disease is unnew embryonic neurons. Transplantation of fetal dopaknown. Viral infections, environmental toxins, and oxidaminergic neurons into rodent models of Parkinson's distive stress induced by dopamine metabolites, are all ease was pioneered in the early 1980s (Bjo ¨rklund and suspected. In contrast, the consequence of dopaminer- Stenevi, 1979;Perlow et al., 1979). In these initial experigic neuron loss for the neural circuits that control movements, approximately 150,000 ventral midbrain neural ment is well understood. The dopaminergic neurons are