Glycine receptors in the striatum, globus pallidus, and substantia nigra of the human brain: an immunohistochemical study

Glycine receptors (GlyRs) are heteropentameric chloride ion channels that facilitate fast-response, inhibitory neurotransmission in the mammalian spinal cord and brain. GlyRs have four functional subunits, alpha1-3 and beta, which likely exist in heteromeric alphabeta combinations. Mutations in GlyR alpha1 and beta subunits are well known for their involvement in hyperekplexia, a paroxysmal motor disorder. In this study we present the first detailed immunohistochemical investigation at the regional, cellular, and subcellular levels of GlyRs in the human basal ganglia. The results show that GlyRs are present at the regional level in low concentrations in the striatum and globus pallidus and are present in the highest concentrations in the substantia nigra. At the cellular level, GlyRs are present only in discrete populations of neurons immunoreactive for choline acetyltransferase (ChAT), parvalbumin, and calretinin in the human striatum, on a subpopulation of parvalbumin- and calretinin-positive neurons in the globus pallidus, and in the substantia nigra GlyRs are present on approximately three-fourths of all pars compacta and one-third of all pars reticulata neurons. They also form a distinct band of immunoreactive neurons in the intermedullary layers of the globus pallidus. At the subcellular level in the substantia nigra pars reticulata (SNr), GlyRs show a localized distribution on the soma and dendrites that partially complements but does not overlap with the distribution of gamma-aminobutyric acid (GABA)A receptors. Our results demonstrate the precise cellular and subcellular localization of GlyRs in the human basal ganglia and suggest that glycinergic receptors may play an important complementary role to other inhibitory receptors in modulating cholinergic, dopaminergic, and GABAergic neuronal pathways in the basal ganglia.