Genetic control of number of midbrain dopaminergic neurons in inbred strains of mice: relationship to size and neuronal density of the striatum.

The activity of tyrosine hydroxylase [TyrHase; tyrosine-3-monooxygenase; L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] is 20% less in whole midbrain of CBA/J mice than BALB/cJ mice and is paralleled by a comparable difference in the number of dopaminergic neurons in which the enzyme can be detected immunocytochemically. The strain-dependent difference in numbers of TyrHase-containing neurons and of TyrHase activity is not homogeneous in the midbrain but is restricted (along the rostral-caudal axis) to the medial one-third, where almost 2-fold variations are found. The volume of the striatum, a major projection field of midbrain dopamine neurons, is 20% smaller in CBA/J than in BALB/cJ mice; the difference is regional and is concentrated in the caudal half. Because the packing density of intrinsic neurons of the striatum is similar in both strains, CBA/J mice contain 20% fewer neurons than do BALB/cJ mice. The activities of TryHase and of choline acetyltransferase (ChoAcTase; acetyl-CoA:choline-O-acetyltransferase, EC 2.3.1.6) in the whole striatum of CBA/J mice are less than in BALB/cJ. The strain-dependent differences in midbrain TyrHase activity are due to variations in the number of dopamine neurons and directly correlate with differences in the number of striatal cholinergic neurons. There is genetic control of the number of neurons of a neurochemically specific class in the mammalian brain.