The role of GABA in the early neuronal development

A large body of experimental evidences demonstrates that GABA signaling possess an inherent capability for potent regulation of almost all steps of neuronal differentiation and neural tissue formation. The transient GABA production is an inherent feature of many differentiating neuronal populations, regardless of the future neurotransmitter phenotype. While in the mature CNS GABA acts mainly as a synaptic neurotransmitter and elicits phasic responses, in the developing nervous tissue GABA acts as an autocrine/paracrine signal molecule and its main roles are executed through tonic signaling. In young differentiating neurons, most important effects of GABA are mediated through GABA(A) receptors and result in membrane depolarization, and in an increased [Ca2+](I), which in turn can stimulate multiple cellular processes. GABA(B) receptor-mediated effects, which can cause hyperpolarization and reduce [Ca2+](I), appear in later phases of tissue genesis, and seem to balance GABA(A) signaling. The effects of GABA had been demonstrated in the entire period of neural tissue genesis, from proliferation, through migration and differentiation of neuronal precursors, up to the synapse formation and circuit refinement by maturing neurons. The most intriguing developmental role that has been attributed to GABA is the generation and maintenance of activity waves in the period of functional network formation.