Pre- and postnatal development of dopaminergic neuron numbers in the male and female mouse midbrain

Quantitative information about dopaminergic neuron numbers in the mesencephalon is needed to assess the significance of physiological cell death in the regulation of the development of this neural system. Therefore, stereological techniques were applied to determine absolute numbers of mesencephalic neurons immunoreactive to tyrosine hydroxylase during the ontogenetic period between embryonic day (E) 13 and postnatal day (P) 90. Male and female CBA/J mice were examined separately. The most rapid development with a 2.5-fold increase of total counts of immunostained cells per midbrain took place in the prenatal period. Beginning at E21, immunostained cells were counted separately in their three main locations, substantia nigra (SN), ventral tegmental area (VTA), and retrorubral field (RRF). Neuron numbers in RRF and VTA reached adult levels perinatally. In contrast, counts of immunostained cells in SN continued to increase postnatally. The only sign of cell loss was a transient decrease in VTA cell numbers (but not in total numbers of immunostained midbrain neurons) between E21 and P14. There were no statistically significant sex differences in cell numbers at any time point investigated. It is concluded that physiological cell death is not a major factor in the developmental regulation of dopaminergic cell numbers in the mouse midbrain.