The output neurones and the dopaminergic neurones of the substantia nigra receive a GABA‐Containing input from the globus pallidus in the rat
Authors: Smith Y. , Bolam J. P. 
Published: January 2005

AbstractOne of the major pathways of information flow through the basal ganglia is the pallidonigrofugal system. In order to better understand this system in the rat, experiments have been performed to study the topography, synaptic organization, and neurotransmitter content of the pallidonigral projection and to determine whether the pallidonigral neurones make direct synaptic contacts with nigrofugal cells. This was achieved by combining the anterograde transport of the lectin Phaseolus vulgaris‐leucoagglutinin (PHA‐L) with the retrograde transport of lectin‐conjugated horseradish peroxidase (WGA‐HRP), postembedding immunocytochemistry for gamma‐aminobutyric acid (GABA), and pre‐embedding immunocytochemistry for tyrosine hydroxylase (TH). Following injections of PHA‐L in different regions of the lateral part of the globus pallidus, a substantial number of immunoreactive fibres and terminals occurred in the ipsilateral substantia nigra reticulata (SNr). The immunoreactive elements were distributed according to a rostral to medial and caudal to lateral topography. Injections that were restricted to the medial tip of the globus pallidus led to the anterograde labeling of a small number of fibres that were sparsely distributed in the SNr. The most characteristic feature of the pallidonigral fibres was the presence of large varicosities that were often grouped to form pericellular baskets. Injections of WGA‐HRP in the ventromedial thalamic nucleus, superior colliculus, or midbrain tegmentum, including the pedunculopontine nucleus, showed that the perikarya and primary dendrites of the output cells of the SNr were often surrounded by the large pallidonigral varicosities. The number of varicosities surrounding a single cell varied from 2–12. Electron microscopic analysis showed that the varicosities contained round or slightly pleomorphic vesicles and numerous mitochondria and that they established symmetrical synaptic contacts. Quantitative measurements revealed that the varicosities had a maximum diameter varying from 0.5 to 2.5 μm and a mean cross‐sectional area of 0.76 ± 0.25 μm2 (N = 237, mean ± S.D.). The postsynaptic structures of the pallidonigral varicosities included perikarya (48%), large dendrites (38%), and small dendrites (14%). A large proportion of these postsynaptic targets were retrogradely labeled after injection of WGA‐HRP in the ventromedial thalamic nucleus, superior colliculus, or midbrain tegmentum. Postembedding immunocytochemistry was used to show that the pallidonigral axons and terminals in contact with nigrofugal neurones displayed GABA immunoreactivity. The use of a double immunocytochemical method revealed, that in addition to the nondopaminergic SNr output neurones, the dendrites and perikarya of the dopaminergic cells of the substantia nigra pars compacta (SNc) receive an input from the globus pallidus. However, this input is very much sparser than that to the cells of the SNr.In conclusion, the results of our study (1) demonstrate that the pallidonigral projection arises predominantly from cells in the lateral third of the globus pallidus and arborizes in the SNr according to a rostral to medial and caudal to lateral topography, (2) suggest that the pallidonigral neurones exert a powerful control over the output neurones of the SNr, (3) reveal that the pallidonigral projection is a major source of GABA in the rat substantia nigra, and (4) show that the perikarya and dendrites of the dopaminergic cells in the SNc receive an input albeit sparse from the globus pallidus.