title: Differential expression of metabotropic glutamate and GABA receptors at neocortical glutamatergic and GABAergic axon terminals.
abstract: Metabotropic glutamate (Glu) receptors (mGluRs) and GABAB receptors are highly expressed at presynaptic sites. To verify the possibility that the two classes of metabotropic receptors contribute to axon terminals heterogeneity, we studied the localization of mGluR1α, mGluR5, mGluR2/3, mGluR7, and GABAB1 in VGLUT1-, VGLUT2-, and VGAT- positive terminals in the cerebral cortex of adult rats. VGLUT1-positive puncta expressed mGluR1α (∼5%), mGluR5 (∼6%), mGluR2/3 (∼22%), mGluR7 (∼17%), and GABAB1 (∼40%); VGLUT2-positive terminals expressed mGluR1α (∼10%), mGluR5 (∼11%), mGluR2/3 (∼20%), mGluR7 (∼28%), and GABAB1 (∼25%); whereas VGAT-positive puncta expressed mGluR1α (∼27%), mGluR5 (∼24%), mGluR2/3 (∼38%), mGluR7 (∼31%), and GABAB1 (∼19%). Control experiments ruled out the possibility that postsynaptic mGluRs and GABAB1 might have significantly biased our results. We also performed functional assays in synaptosomal preparations, and showed that all agonists modify Glu and GABA levels, which return to baseline upon exposure to antagonists. Overall, these findings indicate that mGluR1α, mGluR5, mGluR2/3, mGluR7, and GABAB1 expression differ significantly between glutamatergic and GABAergic axon terminals, and that the robust expression of heteroreceptors may contribute to the homeostatic regulation of the balance between excitation and inhibition.
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, Istituto Nazionale di Riposo e Cura per Anziani - Istituto di Ricovero e Cura a Carattere Scientifico Ancona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Bragina
authors.affiliation: Department of Pharmacy, Unit of Pharmacology and Toxicology, University of Genoa Genoa, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bonifacino
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: Bassi
authors.affiliation: Department of Pharmacy, Unit of Pharmacology and Toxicology, University of Genoa Genoa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Milanese
authors.affiliation: Department of Pharmacy, Unit of Pharmacology and Toxicology, University of Genoa Genoa, Italy ; Center of Excellence for Biomedical Research, University of Genoa Genoa, Italy.
authors.forename: Giambattista
authors.initials: G
authors.lastname: Bonanno
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, Istituto Nazionale di Riposo e Cura per Anziani - Istituto di Ricovero e Cura a Carattere Scientifico Ancona, Italy ; Fondazione di Medicina Molecolare, Università Politecnica delle Marche Ancona, Italy.
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Conti
keywords: GABA; autoreceptors; cerebral cortex; glutamate; heteroreceptors; metabotropic receptors