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Central Role of GABA in Neuron–Glia Interactions

The major types of glial cells—astrocytes, microglia, and cells of the oligodendroglial lineage—are known to express functional metabotropic and ionotropic GABA receptors. Neuronal signaling mechanisms allowing for the activation of these receptors in glia are probably as complex as those described among neurons and involve synaptic and extrasynaptic transmission modes. In addition, astrocytes can signal back to neurons by releasing GABA, probably through unconventional nonvesicular mechanisms. The decryption of the roles played by GABAergic signaling in neuron–glia interactions is only beginning, but it has been suggested that activation of glial cells by GABA influences important functions of the brain such as neuronal activity, differentiation, myelination, and neuroprotection. This review discusses the cellular mechanisms allowing the major types of glial cells to sense and transmit GABAergic signals and gives an overview of potential roles of this signaling pathway in developing and mature brains.