The time course of developmental cell death in phenotypically defined dopaminergic neurons of the substantia nigra.

We have previously shown that apoptotic natural cell death occurs within the substantia nigra (SN) pars compacta of the rat postnatally. However, the occurrence of natural cell death in phenotypically defined dopaminergic neurons has not previously been identified, nor has its time course been defined in pre- or postnatal development. We therefore examined the SN at intervals from E19 to P28 using immunostaining for tyrosine hydroxylase with a Nissl counterstain to identify intranuclear apoptotic chromatin clumps. We have found that natural cell death in dopaminergic neurons is biphasic. An initial, broad peak begins at E20, reaches maximum at P2, and abates by P8. A second peak occurs at P14. We conclude that most of the natural cell death in this neuronal population occurs in the early postnatal period.