AMPA receptor activation induces GABA release from neurons migrating tangentially in the intermediate zone of embryonic rat neocortex

Abstract

In the intermediate zone of the embryonic rodent neocortex, neurons migrating tangentially from the basal ganglia express both functional amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors and gamma-aminobutyric acid (GABA). To test the hypothesis of GABA release triggered by AMPA receptor activation, we used whole-hemisphere cultures prepared from rat embryos (day 15). We observed a marked decrease in the number of detectable GABA-positive cells in the intermediate zone after exposure to T-AMPA. This effect was blocked by coapplying GYKI 53655, an AMPA receptor antagonist. The decrease in GABA immunolabelling induced by T-AMPA did not require extracellular calcium. In contrast, it was abolished after sodium substitution by choline, or after coapplication of nipecotic acid, a GABA transporter inhibitor. Exposure to high potassium reduced the number of detectable GABA-positive cells. These results are compatible with carrier-mediated GABA release consecutive to sodium influx. GABA released from neurons migrating tangentially in the intermediate zone after AMPA receptor activation may influence neighbouring elements including radially migrating postmitotic neurons, proliferating progenitors and possibly the tangential cells themselves.