PT - JOURNAL ARTICLE AU - Rogelio O. Arellano AU - Maria Victoria Sanchez-Gomez AU - Elena Alberdi AU - Manuel Canedo-Antelo AU - Juan Carlos Chara AU - Aitor Palomino AU - Alberto Perez-Samartin AU - Carlos Matute TI - Axon-to-Glia Interaction Regulates Gaba<sub>A</sub> Receptor Expression in Oligodendrocytes AID - 10.1124/mol.115.100594 DP - 2015 Jan 01 TA - Molecular Pharmacology PG - mol.115.100594 4099 - http://molpharm.aspetjournals.org/content/early/2015/11/04/mol.115.100594.short 4100 - http://molpharm.aspetjournals.org/content/early/2015/11/04/mol.115.100594.full AB - Myelination requires oligodendrocyte-neuron communication, and both neurotransmitters and contact interactions are essential for this process. Oligodendrocytes are endowed with neurotransmitter receptors whose expression levels and properties may change during myelination. However, only scant information is availble about the extent and timing of these changes or how they are regulated by oligodendrocyte-neuron interactions. Here, we used electrophysiology to study the expression of ionotropic GABA (γ-aminobutyric acid), glutamate, and ATP receptors in oligodendrocytes derived from the optic nerve and forebrain cultured either alone or in the presence of dorsal root ganglion neurons. We observed that oligodendrocytes from both regions responded to these transmitters at one day in culture. After the first day in culture, however, GABA sensitivity diminished drastically to less than 10%, while that of glutamate and ATP remained constant. In contrast, the GABA response amplitude was sustained and remained stable in oligodendrocytes co-cultured with dorsal root ganglion neurons. Immunochemistry and pharmacological properties of the responses indicated that they were mediated by distinctive GABAA receptors and that, in co-culture with neurons, the oligodendrocytes bearing the receptors were those in direct contact with axons. These results reveal that GABAA receptor regulation in oligodendrocytes is driven by axonal cues, and that GABA signaling may play a role in myelination and/or during axon-glia recognition.