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. 2015 Sep 4:9:345.
doi: 10.3389/fncel.2015.00345. eCollection 2015.

Differential expression of metabotropic glutamate and GABA receptors at neocortical glutamatergic and GABAergic axon terminals

Luca Bragina  1 , Tiziana Bonifacino  2 , Silvia Bassi  3 , Marco Milanese  2 , Giambattista Bonanno  4 , Fiorenzo Conti  5
Affiliations

Differential expression of metabotropic glutamate and GABA receptors at neocortical glutamatergic and GABAergic axon terminals

Luca Bragina et al. Front Cell Neurosci. .

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.

Keywords: GABA; autoreceptors; cerebral cortex; glutamate; heteroreceptors; metabotropic receptors.

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Figures

FIGURE 1
FIGURE 1
VGLUT1, VGLUT2, VGAT, mGluR1α, mGluR5, mGluR2/3, mGluR7, and GABAB1 antibodies recognized bands of ∼55, 60, 57, 140, 132, 100, and 190, 97, 100, and 132 kDa in the order in crude membrane fractions of rat cerebral cortex.
FIGURE 2
FIGURE 2
Expression of metabotropic glutamate and GABA receptors in cerebral cortex. The figure shows representative images from the VGLUT1 series (first row), the VGLUT2 series (second row), and the VGAT series (third row). Puncta were considered double-labeled (arrows) when overlap was virtually complete or when a given punctum was entirely included in the other puncta. Bar: 4 μm.
FIGURE 3
FIGURE 3
Expression of mGluR1α, mGluR5, mGluR2/3, mGluR7, and GABAB1 in VGLUT1+, VGLUT2+, and VGAT+ axon terminals in cerebral cortex. Values are mean ± SEM; ∗∗p < 0.01, ∗∗∗p < 0.001.
FIGURE 4
FIGURE 4
Control analysis of confocal microscopy images. VGLUT1/GABAB1 in molecular layer of cerebellum (Cb) and in ventrobasal complex (VB). Puncta were considered double-labeled when overlap was virtually complete or when a given punctum was entirely included in the other puncta (arrows in third and fourth columns). Puncta that did not meet these criteria (arrowheads) were not considered double-labeled; Bars: 2 μm.
FIGURE 5
FIGURE 5
Effect of agonists and antagonists of mGluR1/5, mGluR2/3, mGluR7, or GABAB receptors on the release of endogenous glutamate (A) and GABA (B) from rat parietal cortex synaptosomes. Data are expressed as percent of the spontaneous outflow (mGluR1/5 effect) or of the 15 mM KCl-evoked overflow (mGluR2/3/7 and GABAB effects). White and gray columns refer to agonist or agonist + antagonist administration. Data are means ± SEM of 6–10 independent experiments (6–10 rats per group). ∗p < 0.05 and ∗∗p < 0.01 vs. controls.
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References

    1. Alonso-Nanclares L., Minelli A., Melone M., Edwards R. H., Defelipe J., Conti F. (2004). Perisomatic glutamatergic axon terminals: a novel feature of cortical synaptology revealed by vesicular glutamate transporter 1 immunostaining. Neuroscience 123 547–556. 10.1016/j.neuroscience.2003.09.033 - DOI - PubMed
    1. Atwood H. L., Karunanithi S. (2002). Diversification of synaptic strength: presynaptic elements. Nat. Rev. Neurosci. 3 497–516. 10.1038/nrn876 - DOI - PubMed
    1. Battaglia G., Monn J. A., Schoepp D. D. (1997). In vivo inhibition of veratridine-evoked release of striatal excitatory amino acids by the group II metabotropic glutamate receptor agonist LY354740 in rats. Neurosci. Lett. 229 161–164. 10.1016/S0304-3940(97)00442-4 - DOI - PubMed
    1. Bellocchio E. E., Hu H., Pohorille A., Chan J., Pickel V. M., Edwards R. H. (1998). The localization of the brain-specific inorganic phosphate transporter suggests a specific presynaptic role in glutamatergic transmission. J. Neurosci. 18 8648–8659. - PMC - PubMed
    1. Bogen I. L., Boulland J. L., Mariussen E., Wright M. S., Fonnum F., Kao H. T., et al. (2006). Absence of synapsin I and II is accompanied by decreases in vesicular transport of specific neurotransmitters. J. Neurochem. 96 1458–1466. 10.1111/j.1471-4159.2005.03636.x - DOI - PubMed

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