Fig. 1.

GABA cycling between interneurons, cells of the oligodendrocyte (OL) lineage, and astrocytes. A In the central nervous system, interneurons form an intricate signaling network with cells of the OL lineage, i.e., myelinating OLs and their precursors (OPCs), and with perisynaptic as well as perinodal processes of astrocytes. B In the synaptic microenvironment, extracellular glutamate is converted into glutamine in astrocytes by glutamine synthetase (GS). After release, glutamine is taken up by interneurons and transformed into GABA by the glutamate decarboxylases GAD65 and/or GAD67. Upon action potential arrival, GABA is released into the synaptic cleft by vesicles expressing GABA transporters (vGAT). After binding to postsynaptic neuronal GABA_A and/or GABA_B receptors, GABA induces postsynaptic neuronal hyperpolarization. But neuron-released GABA can also act on the GABA receptors of OPCs modulating axonal myelination. In addition, extrasynaptic GABA is taken up by neuronal GAT1 and astroglial GAT3 transporters. Both transporters, however, are also expressed by OPCs, but functional studies are still required to determine their roles. C Also, OLs can express GS to produce glutamine. The latter might be transported to myelinated axons, where it can be converted into GABA. Additional experiments are still required to test this hypothesis.