Brainstem dopaminergic, cholinergic and serotoninergic afferents to the pallidum in the squirrel monkey

Abstract

The retrograde tracer cholera toxin B subunit (CTb) was used in combination with immunohistochemistry for tyrosine hydroxylase (TH), calbindin D-28k (CaBP), choline acetyltransferase (ChAT) and 5-hydroxytryptamine (5-HT) to determine the distribution and relative proportion of brainstem chemospecific neurons that project to the pallidum in the squirrel monkey ( Saimiri sciureus). Large injections of CTb involving both pallidal segments produce numerous retrogradely labeled neurons in the substantia nigra (SN), the pedunculopontine tegmental nucleus (PPN) and the dorsal raphe nucleus (DR). Labeled neurons are distributed uniformly in SN with a slight numerical increase at the junction between the pars compacta (SNc) and the ventral tegmental area (VTA). Retrogradely labeled neurons abound also in PPN, principally in its pars dissipata, whereas other CTb-labeled cells are scattered throughout the rostrocaudal extent of DR. After CTb injection involving specifically the internal pallidal segment (GPi), the same pattern of cell distribution is found in SN, PPN and DR, except that the number of retrogradely labeled cells is lower than after large pallidal complex injections. Approximately 70% of all CTb-labeled neurons in SNc-VTA complex display TH immunoreactivity, whereas 20% are immunoreactive for CaBP. About 39% of all retrogradely labeled neurons in PPN are immunoreactive for ChAT, whereas approximately 38% of the labeled neurons in DR display 5-HT immunoreactivity. Following CTb injection in the external pallidal segment (GPe), the number of labeled cells is much smaller than after GPi injection. The majority of CTb-labeled cells in SNc-VTA complex are located in the lateral half of SNc and approximately 93% of these neurons display TH immunoreactivity compared to 10% that are immunoreactive for CaBP; very few CTb-labeled cells occur in PPN. Retrogradely labeled cells in DR are located more laterally than those that projects to the GPi and about 25% of them are immunoreactive for 5-HT. These results suggest that, in addition to their action at striatal and/or nigral levels, the brainstem dopaminergic, cholinergic and serotoninergic neurons influence the output of the primate basal ganglia by acting directly upon GPi neurons.