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.
Highlights
Presynaptic mechanisms affecting neurotransmitter release play a key role in modulating synaptic strength and plasticity (Atwood and Karunanithi, 2002); they may be associated to molecular heterogeneity of axon terminals (Staple et al, 2000)
VGLUT1, VGLUT2, mGluR1α, mGluR5, mGluR2/3, mGluR7, and GABAB1 immunoreactivities were as described in previous studies (Reid et al, 1995; Romano et al, 1995; Petralia et al, 1996; Bellocchio et al, 1998; Chaudhry et al, 1998; Kinoshita et al, 1998; Kaneko et al, 2002; Kulik et al, 2002; Lopez-Bendito et al, 2002; Minelli et al, 2003; Muly et al, 2003; Alonso-Nanclares et al, 2004; Conti et al, 2005)
These antibodies were, used to verify whether mGluR1α, mGluR5, mGluR2/3, mGluR7, and GABAB1 are differentially expressed in VGLUT1+, VGLUT2+, and VGAT+ axon terminals
Summary
Presynaptic mechanisms affecting neurotransmitter release play a key role in modulating synaptic strength and plasticity (Atwood and Karunanithi, 2002); they may be associated to molecular heterogeneity of axon terminals (Staple et al, 2000). GABAB1 is expressed presynaptically in several brain regions (Kulik et al, 2002, 2003; Lujan et al, 2004; McDonald et al, 2004; Lacey et al, 2005; Lujan and Shigemoto, 2006), including the cerebral cortex, where it is localized at both symmetric and asymmetric synapses (Gonchar et al, 2001; Lopez-Bendito et al, 2002). One major function of presynaptic GABAB receptors is modulation of neurotransmitter release, as they inhibit the release of both glutamate and GABA in different regions of the CNS, including cerebral cortex (Bowery et al, 1980; Bonanno and Raiteri, 1993)
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