Fig. (2) .

The developmental switch in chloride cotransporter (CCC) expression drives the functional switch of GABA_A receptors from depolarizing to hyperpolarizing.The developmental increase in KCC2 and, in certain tissues, the decrease in NKCC1 triggers the switch from depolarizing to hyperpolarizing GABA_Aergic signaling [247, 261]. GABA-mediated depolarizations activate L-type voltage sensitive calcium channels(L-VSCC) and release the Mg++ block of NMDA receptors, increasing intracellular Ca++. This can activate calciumregulated signaling pathways, which are important in neuronal development, migration, proliferation, synaptogenesis and differentiation. The GABA-mediated activation of calcium signaling does not occur in neurons with hyperpolarizing GABA_A receptor responses.