Functional significance of co-localization of GABA and Glu in nerve terminals: a hypothesis.

Salient features of the co-transmission by GABA and Glu in neural signaling are summarized. Experimental data have been accumulating which demonstrate; i) GABA-immunoreactivity in and GABA-release from constitutively Gluergic hippocampal mossy fibre terminals, ii) plasticity of the GABAergic phenotype of constitutively Gluergic granule cells of the Dentate Gyrus, iii) expression of GABA(A) receptor gamma(3) subunit in the mossy fibre termination zone in the CA3 subfield, iv) co-labeling of terminals for GABA and Glu in the retina, brain stem and spinal cord, and v) functional compatibility of vesicular Glu (VGLUT3) and GABA (VIAAT) transporters. It is not clear, however, whether or not Glu and GABA are released from the same terminals, and packaged in the same vesicles. Using multiple transmitters neurons may serve to reduce the metabolic cost and errors of signaling.