title: Axon-to-Glia Interaction Regulates GABAA Receptor Expression in Oligodendrocytes.
abstract: 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 available 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, 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 1 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 cocultured with dorsal root ganglion neurons. Immunochemistry and pharmacological properties of the responses indicated that they were mediated by distinctive GABAA receptors and that in coculture 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.
authors.affiliation: Achucarro Basque Center for Neuroscience, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, and Departamento de Neurociencias, Universidad del País Vasco, Leioa, Spain (R.O.A., M.V.S.-G., E.A., M.C.-A., J.C.C., A.P., A.P.-S., C.M.); and Instituto de Neurobiología, Laboratorio de Neurofisiología Celular, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, México (R.O.A.) arellano.ostoa@comunidad.unam.mx carlos.matute@ehu.es.
authors.forename: Rogelio O
authors.initials: RO
authors.lastname: Arellano
authors.affiliation: Achucarro Basque Center for Neuroscience, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, and Departamento de Neurociencias, Universidad del País Vasco, Leioa, Spain (R.O.A., M.V.S.-G., E.A., M.C.-A., J.C.C., A.P., A.P.-S., C.M.); and Instituto de Neurobiología, Laboratorio de Neurofisiología Celular, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, México (R.O.A.).
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Sánchez-Gómez
authors.affiliation: Achucarro Basque Center for Neuroscience, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, and Departamento de Neurociencias, Universidad del País Vasco, Leioa, Spain (R.O.A., M.V.S.-G., E.A., M.C.-A., J.C.C., A.P., A.P.-S., C.M.); and Instituto de Neurobiología, Laboratorio de Neurofisiología Celular, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, México (R.O.A.).
authors.forename: Elena
authors.initials: E
authors.lastname: Alberdi
authors.affiliation: Achucarro Basque Center for Neuroscience, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, and Departamento de Neurociencias, Universidad del País Vasco, Leioa, Spain (R.O.A., M.V.S.-G., E.A., M.C.-A., J.C.C., A.P., A.P.-S., C.M.); and Instituto de Neurobiología, Laboratorio de Neurofisiología Celular, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, México (R.O.A.).
authors.forename: Manuel
authors.initials: M
authors.lastname: Canedo-Antelo
authors.affiliation: Achucarro Basque Center for Neuroscience, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, and Departamento de Neurociencias, Universidad del País Vasco, Leioa, Spain (R.O.A., M.V.S.-G., E.A., M.C.-A., J.C.C., A.P., A.P.-S., C.M.); and Instituto de Neurobiología, Laboratorio de Neurofisiología Celular, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, México (R.O.A.).
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Chara
authors.affiliation: Achucarro Basque Center for Neuroscience, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, and Departamento de Neurociencias, Universidad del País Vasco, Leioa, Spain (R.O.A., M.V.S.-G., E.A., M.C.-A., J.C.C., A.P., A.P.-S., C.M.); and Instituto de Neurobiología, Laboratorio de Neurofisiología Celular, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, México (R.O.A.).
authors.forename: Aitor
authors.initials: A
authors.lastname: Palomino
authors.affiliation: Achucarro Basque Center for Neuroscience, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, and Departamento de Neurociencias, Universidad del País Vasco, Leioa, Spain (R.O.A., M.V.S.-G., E.A., M.C.-A., J.C.C., A.P., A.P.-S., C.M.); and Instituto de Neurobiología, Laboratorio de Neurofisiología Celular, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, México (R.O.A.).
authors.forename: Alberto
authors.initials: A
authors.lastname: Pérez-Samartín
authors.affiliation: Achucarro Basque Center for Neuroscience, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, and Departamento de Neurociencias, Universidad del País Vasco, Leioa, Spain (R.O.A., M.V.S.-G., E.A., M.C.-A., J.C.C., A.P., A.P.-S., C.M.); and Instituto de Neurobiología, Laboratorio de Neurofisiología Celular, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, México (R.O.A.) arellano.ostoa@comunidad.unam.mx carlos.matute@ehu.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: Matute
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000096:biosynthesis*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid