Differential localization of NADPH-diaphorase and calbindin-D28k within the cholinergic neurons of the basal forebrain, striatum and brainstem in the rat, monkey, baboon and human.

The localization of Calbindin-D28k and NADPH-diaphorase in the cholinergic neurons of the basal forebrain, striatum and brainstem was investigated in the rat, monkey, baboon and human using calbindin and choline acetyltransferase immunohistochemistry and NADPH-diaphorase histochemistry. Considerable regional and species-specific variations were observed. Double-stained sections demonstrated that NADPH-diaphorase activity occurred in as much as 20-30% of basal forebrain cholinergic neurons in the rat but in virtually none of those neurons in the monkey, baboon or human. In all of the species studied, virtually every cholinergic neuron within the pedunculopontine and laterodorsal tegmental nuclei contained NADPH-diaphorase activity, while none of the cholinergic neurons of the striatum did so. In the rat brain, calbindin immunoreactivity was not present in any of the cholinergic neurons of the basal forebrain, while in the primate brain virtually all of the basal forebrain cholinergic neurons were also calbindin-positive. None of the cholinergic neurons of the striatum, pedunculopontine nucleus or laterodorsal tegmental nucleus were found to be calbindin-positive in any of the species examined. These results demonstrate major species-specific differences in the cytochemical signatures of the basal forebrain cholinergic neurons, in contrast to the cholinergic neurons of the striatum and brainstem, which displayed little interspecies variation with respect to the markers that were used in this study. Our findings also suggest that caution must be exercised in using results from studies of rodent basal forebrain cholinergic systems to infer the role of this system in the primate brain.