Glutamate and GABA mediate most of the excitatory and inhibitory synaptic transmission; they are taken up and accumulated in synaptic vesicles by specific vesicular transporters named VGLUT1-3 and VGAT, respectively.

We demonstrated that in neocortex VGLUT1 and VGAT are co-expressed in a subset of axon terminals forming both symmetric and asymmetric synapses, that VGLUT1 and VGAT are sorted to the same vesicles and that at synapses expressing the vesicular heterotransporter vesicles participate in the exo-endocytotic cycle (Fattorini et al., J Neurochem. 110:1538-1546).

Here, we asked whether this population of terminals is affected by perturbations of excitation-inhibition balance. To this end, we used rat primary cultures of embryonic cortical neurons exposed (from 14 DIV) to molecules which interfere with either glutamatergic or GABAergic synaptic transmission: GluR antagonists AP5 (100 mM) and CNQX (20 mM) for 1 week; the GABAA antagonist bicuculline (100 mM) for 1 week; valproic acid (1 mM, 24 hours); and glutamate (50 mM, 24 hours). Sister cultures were randomly assigned to control and experimental groups. Results showed that chronic blockade of excitatory transmission results in a significant reduction of cortical axon terminals coexpressing VGLUT1 and VGAT, whereas chronic blockade of inhibitory transmission determines a significant increase of this population. Finally, valproic acid and glutamate do not alter the degree of VGLUT1-VGAT colocalization.