title: Plasma membrane transporters GAT-1 and GAT-3 contribute to heterogeneity of GABAergic synapses in neocortex.
abstract: Cortical GABAergic synapses exhibit a high degree of molecular, anatomical and functional heterogeneity of their neurons of origins, presynaptic mechanisms, receptors, and scaffolding proteins. GABA transporters (GATs) have an important role in regulating GABA levels; among them, GAT-1 and GAT-3 play a prominent role in modulating tonic and phasic GABAAR-mediated inhibition. We asked whether GAT-1 and GAT-3 contribute to generating heterogeneity by studying their ultrastructural localization at cortical symmetric synapses using pre- and post-embedding electron microcopy. GAT-1 and GAT-3 staining at symmetric synapses showed that in some cases the transporters were localized exclusively over axon terminals; in others they were in both axon terminals and perisynaptic astrocytic processes; and in some others GAT-1 and GAT-3 were in perisynaptic astrocytic processes only. Moreover, we showed that the organizational pattern of GAT-1, but not of GAT-3, exhibits a certain degree of specificity related to the post-synaptic target of GABAergic synapses. These findings show that symmetric synapses expressing GAT-1 or GAT-3 are heterogeneous, and indicate that plasma membrane transporters can contribute to synaptic heterogeneity.
authors.affiliation: Section of Neuroscience and Cell Biology, Department of Experimental and Clinical Medicine, Università Politecnica delle Marche Ancona, Italy ; Center for Neurobiology of Aging, INRCA IRCCS Ancona, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Melone
authors.affiliation: Section of Neuroscience and Cell Biology, Department of Experimental and Clinical Medicine, Università Politecnica delle Marche Ancona, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ciappelloni
authors.affiliation: Section of Neuroscience and Cell Biology, Department of Experimental and Clinical Medicine, Università Politecnica delle Marche Ancona, Italy ; Center for Neurobiology of Aging, INRCA IRCCS Ancona, Italy ; Foundation for Molecular Medicine, Università Politecnica delle Marche Ancona, Italy.
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Conti
keywords: GABA; GABA transporters; GAT-1; GAT-3; heterogeneity; symmetric synapses