NEURONAL AND GLIAL LOCALIZATION OF GAT-1, A HIGH-AFFINITY GAMMA-AMINOBUTYRIC-ACID PLASMA-MEMBRANE TRANSPORTER, IN HUMAN CEREBRAL-CORTEX - WITH A NOTE ON ITS DISTRIBUTION IN MONKEY CORTEX

High-affinity gamma-aminobutyric (GABA) plasma membrane transporters ( GATs) influence the action of GABA, the main inhibitory neurotransmitt er in the human cerebral cortex. In this study, the cellular expressio n of GAT-1, the main cortical GABA transporter, was investigated in th e human cerebral cortex by using immunocytochemistry with affinity-pur ified polyclonal antibodies directed to the C-terminus of rat GAT-1. I n temporal and prefrontal association cortex (Brodmann's areas 21 and 46) and in cingulofrontal transition cortex (area 32), specific GAT-1 immunoreactivity (ir) was localized to numerous puncta and fibers in a ll cortical layers. GAT-1(+) puncta were distributed homogeneously in all cortical layers, although they were slightly more numerous in laye rs II-TV, and appeared to have a preferential relationship to the soma ta and proximal dendrites of unlabeled pyramidal cells, even though, i n many cases, they were also observed around nonpyramidal cells. Elect ron microscopic observations showed that GAT-1(+) puncta were axon ter minals that formed exclusively symmetric synapses. In addition, some d istal astrocytic processes also contained immunoreaction product. Anal ysis of the patterns of GAT-1 labeling in temporal and prefrontal asso ciation areas (21 and 46), in cingulofrontal transition areas (32), an d in somatic sensory and motor areas (1 and 4) of the monkey cortex re vealed that its distribution varies according to the type of cortex ex amined and indicated that the distribution of GAT-1 is similar in anat omically corresponding areas of different species. The present study d emonstrates that, in the human homotypical cortex, GAT-1 is expressed by both inhibitory axon terminals and astrocytic processes. This local ization of GAT-1 is compatible with a major role for this transporter in GABA uptake at GABAergic synapses and suggests that GAT-1 may contr ibute to determining GABA levels in the extracellular space. (C) 1998 Wiley-Liss, Inc.