The dendritic dopamine projection of the substantia nigra: phenotypic denominator of weaver gene action in hetero- and homozygosity.

While cerebellar granule cell migration and survival are affected by the weaver (wv) mutation both in the heterozygous and homozygous states, the dopamine (DA) deficit of the nigrostriatal projection has been shown to involve only midbrain DA cell bodies and nigrostriatal DA axons of homozygous mutants. We have identified a cellular site which is defective in the mesencephalic DA system of mice both heterozygous and homozygous for the wv gene. That deficit involves the dendritic DA projection which extends from the substantia nigra pars compacta (SNc) into the pars reticulata (SNr). In the midbrain of heterozygotes, dopaminergic dendrites are reduced by 60% at 20 days of age, when DA neurone number in the midbrain, DA content in the neostriatum and pattern of synaptic connectivity of nigrostriatal axon terminals are normal. At the same age, the deficit of dopaminergic dendrites in the SNr of homozygotes (76%) is disproportionate to the loss of DA cell bodies (42%). These findings: (a) may provide clues to the aetiopathogenetic mechanisms of wv gene operation; and (b) may explain the generalised convulsions intermittently manifested by weaver heterozygotes, as the SN has been implicated in the pathophysiology of experimental seizures.