The effect of forebrain lesions in the neonatal rat: survival of midbrain dopaminergic neurons and the crossed nigrostriatal projection.

Lesions were placed in the striatum and the olfactory tubercle of 1-day-old rat pups. Control and experimental animals were raised to adulthood. Efferent projections of mesencephalic neurons were examined by injecting the retrograde tracers horseradish peroxidase or Fast Blue into the undamaged striata of some experimental animals. The survival of the mesencephalic dopaminergic neurons was monitored by using immunocytochemical localization of tyrosine hydroxylase. Small lesions in the caudate-putamen had no appreciable effect on the survival of tyrosine hydroxylase-containing neurons in the mesencephalon, but the density of dopaminergic terminals adjacent to the lesion increased in the remaining caudate-putamen. Striatal lesions that involved an estimated area of more than one-third resulted in loss of dopamine neurons of the substantia nigra compacta. Rostral lesions in the striatum affected mostly rostrally positioned neurons in the substantia nigra. Dorsal lesions of the caudate-putamen resulted in disappearance of dorsal A9 neurons. Reduction of the A10 and A8 dopamine neuron groups occurred if the neonatal lesions involved the olfactory tubercle and nucleus accumbens. Some tyrosine hydroxylase-containing neurons persisted even after the largest lesions. These dopaminergic neurons formed a crossed nigrostriatal pathway which was confirmed by retrogradely transported tracers. The density of this crossed projection in the adult appeared unaffected by the neonatal lesion. We concluded that dopaminergic neurons form topographically ordered projections with their targets in the newborn rat. Rearrangement of these fibers appeared limited, but compensatory increase of axon terminal density was evident in partially lesioned target areas.