EARLY DEVELOPMENTAL DESTRUCTION OF TERMINALS IN THE STRIATAL TARGET INDUCES APOPTOSIS IN DOPAMINE NEURONS OF THE SUBSTANTIA-NIGRA

Many developing neural systems with peripheral projections depend on t heir target for trophic support during a critical period of natural ce ll death. Much less is known about central systems. That dopaminergic neurons of the substantia nigra may depend on their target, the striat um, during development is suggested by the presence of a natural apopt otic cell death event in these neurons that can be augmented by an ear ly developmental axon-sparing striatal injury, To further assess the t arget dependence of these neurons, we have used the selective neurotox in B-hydroxydopamine to lesion their terminals within the striatum dur ing development, while sparing intrinsic striatal target neurons. This lesion results in an induction of apoptotic cell death in phenotypica lly defined dopaminergic neurons that appears on the third postlesion day and persists until the tenth, This inducibility of cell death is d ependent on developmental age: it is most marked before postnatal day (PND) 14. As late as PND42, inducibility is still detectable but much less so, In addition, at day 42 the morphology of cell death changes a nd becomes nonapoptotic in some cells. We conclude that terminal injur y during a critical period of postnatal development, like axon-sparing target injury, induces augmented apoptotic death in mesencephalic dop aminergic neurons. These results suggest that these neurons have a per iod of target dependence. Regulation of this dependence is likely to i nfluence the mature adult number of dopaminergic neurons.