GABAergic Afferents Activate Both GABAAand GABABReceptors in Mouse Substantia Nigra Dopaminergic NeuronsIn Vivo

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Abstract
Mostin vivoelectrophysiological studies of substantia nigra have used rats. With the recent proliferation of the use of mice forin vitroneurophysiological studies because of the availability of various genetically modified strains to identify the roles of various channels and proteins in neuronal function, it is crucial to obtain data onin vivoresponses in mice to verify that thein vitroresults reflect functioning of systems comparable with those that have been well studied in rat.Inhibitory responses of rat nigral dopaminergic neurons by stimulation of afferents from striatum, globus pallidus, or pars reticulata have been shown to be mediated predominantly or exclusively by GABAAreceptors. This is puzzling given the substantial expression of GABABreceptors and the ubiquitous appearance of GABABsynaptic responses in rat dopaminergic neuronsin vitro. In the present study, we studied electrically evoked GABAergic inhibition in nigral dopaminergic neurons in C57BL/6J mice. Stimulation of the three major GABAergic inputs elicited stronger and longer-lasting inhibitory responses than those seen in rats. The early inhibition was GABAAmediated, whereas the later component, absent in rats, was GABABmediated and selectively enhanced by GABA uptake inhibition. Striatal-evoked inhibition exhibited a slower onset and a weaker initial component compared with inhibition from globus pallidus or substantia nigra pars reticulata. These results are discussed with respect to differences in the size and neuronal density of the rat and mouse brain and the different sites of synaptic contact of the synapses from the three GABAergic afferents.