Figure 1.

Time-line showing the design of the experiment. All animals received a four-site intrastriatal 6-OHDA lesion at the beginning of the experiment (week 0). After the completion of the first behavioral test session, they were divided into two balanced groups to receive either transplantation of fetal VM tissue (VM TRPL) prepared as single cell suspension or sham operation (week 8). They were then followed for an additional 23 weeks and tested for monitorization of the recovery of motor functions. At 31 weeks, each group was further divided into two behaviorally matched subgroups to receive a second lesion at the level of the MFB to remove the remaining host ascending dopamine projections to the forebrain (mainly the nonstriatal projections originating from the ventral tegmental area), or were sham operated. All four groups of animals were followed for an additional 10 weeks. During this time, the impact of the dopamine depletion in the nonstriatal targets was assessed on behaviors (session 3), all of which had initially showed graft-induced recovery. All tissue was processed for histological analysis at 41 weeks after the first lesion.