Morphogenesis of Rodent Neostriatum Following Early Developmental Dopamine Depletion

Neurons of the neostriatum are organized in anatomically and chemically distinct patch and matrix compartments. Dopaminergic neurons of the substantia nigra and ventral tegmental area provide early input to the embryonic neostriatum and may play an important role in neostriatal morphogenesis. Our group and others have demonstrated early loss of dopaminergic neurons in the Pitx3-deficient aphakia mouse, associated with a >90% reduction in neostriatal dopamine levels and a hypokinetic movement disorder. Here, we show scant or absent dopaminergic fibers in the adult aphakia dorsolateral and medial neostriatum, altering the chemical anatomy of mu-opioid receptor stained patches. Furthermore, neostriatal neuron numbers are comparable in aphakia and wild-type animals, but the volume of the aphakia neostriatum and its neurons is significantly reduced. We propose that early nigrostriatal dopaminergic loss in aphakia mice results in loss of trophic support to the developing neostriatum.