Vesicular GABA transporter mRNA expression in the dentate gyrus and in mossy fiber synaptosomes

In the normal granule cells of the dentate gyrus, glutamate and both gamma -aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD) coexist. GA D expression is increased after seizures, and simultaneous glutamatergic an d GABAergic neurotransmission from the mossy fibers to CA3 appears, support ing the hypothesis that GABA can be released from the mossy fibers. To sust ain GABAergic neurotransmission, the amino acid must be transported into sy naptic vesicles. To address this, using RT-PCR we looked for the presence a nd regulation of expression of the vesicular GABA transporter (VGAT) mRNA i n the dentate gyrus and in mossy fiber synaptosomes of control and kindled rats. We found trace amounts of VGAT mRNA in the dentate gyrus and mossy fi ber synaptosomes of control rats. In the dentate gyrus of kindled rats with several seizures and of control rats subject to one acute seizure, no chan ges were apparent either 1 or 24 h after the seizures. However, repetitive synaptic or antidromic activation of the granule cells in slices of control rats in vitro induces an activity-dependent enhancement of VGAT mRNA expre ssion in the dentate. Surprisingly, in the mossy fiber synaptosomes of seiz ing rats, the levels of VGAT mRNA were significantly higher than in control s. These data show that the granule cells and their mossy fibers, besides c ontaining machinery for the synthesis of GABA, also contain the elements th at support its vesiculation. This further supports the notion that local sy naptic molecular changes enable mossy fibers to release GABA in response to enhanced excitability. (C) 2001 Published by Elsevier Science B.V.