GABA-driven excitatory neurotransmission: gene regulation by excitatory GABA and its possible role in the developing brain

Gamma-aminobutyric acid (GABA) has opposing functions, it acts not only as an inhibitory neurotransmitter in the nervous systems, but also as an excitatory one in early developing neurons. Previous studies reported that the excitatory effects of GABA controlled neuronal activity-dependent gene expression, which contributes to long-lasting changes in neuronal functions such as cell survival, differentiation, and synaptic plasticity. We recently demonstrated that excitatory GABA activated multiple Ca 2+ signaling pathways, mainly via L-type voltage-dependent Ca 2+ channels (L-VDCCs), to activate the transcription of the gene encoding brain-derived neurotrophic factor (BDNF). Since BDNF plays a fundamental role in the expression of various functions by the nervous system, the excitatory GABA-induced expression of the BDNF gene may be important for the neural development of the brain. In this review, we summarized the mechanisms underlying the excitatory GABA-induced expression of the BDNF gene, and proposed the possible roles of its regulation in the early development of the brain, an impairment in which may cause the abnormal development of the brain.