The localization of inhibitory neurotransmitter receptors on dopaminergic neurons of the human substantia nigra.

Abstract

The substantia nigra pars compacta (SNc) is comprised mainly of dopaminergic pigmented neurons arranged in groups, with a small population of nonpigmented neurons scattered among these groups. These different types of neurons possess GABAA, GABAB, and glycine receptors. The SNc-pigmented dopaminergic neurons have postsynaptic GABAA receptors (GABAAR) with a subunit configuration containing alpha3 and gamma2 subunits, with a small population of pigmented neurons containing alpha1 beta2,3 gamma2 subunits. GABAB receptors comprised of R1 and R2 subunits and glycine receptors are also localized on pigmented neurons. In contrast, nonpigmented (mainly parvalbumin positive neurons) located in the SNc are morphologically and neurochemically similar to substantia nigra pars reticulata (SNr) neurons by showing immunoreactivity for parvalbumin and GABAARs containing immunoreactivity for alpha1, alpha3, beta2,3, and gamma2 subunits as well as GABAB R1 and R2 subunits and glycine receptors. Thus, these two neuronal types of the SNc, either pigmented dopaminergic neurons or nonpigmented parvalbumin positive neurons, have similar GABAB and glycine receptor combinations, but differ mainly in the subunit composition of the GABAARs located on their membranes. The different types of GABAARs suggest that GABAergic inputs to these neuronal types operate through GABAARs with different pharmacological and physiological profiles, whereas GABABR and glycine receptors of these cell types are likely to have similar properties.