Diversity of glutamate receptors in glial cells of the mouse optic nerve.

Introduction: Glial cells in the optic nerve express ionotropic glutamate receptors that may contribute to axon-glia communication, yet their functional expression in defined glial populations remains incompletely characterized. We investigated glutamate receptor-mediated responses in identified NG2 glia and astrocytes of the mouse optic nerve. Methods: We used a longitudinal optic nerve slice preparation combined with whole-cell patch-clamp recordings. NG2 glia and astrocytes were identified and electrophysiologically characterized using the transgenic reporter mouse lines hGFAP-eGFP and Cx43-ki-eCFP, respectively. Functional responses to kainic acid (KA), activating AMPA/kainate receptors, and NMDA were assessed at the single-cell level. Results: KA evoked membrane current responses in the majority of NG2 glia, whereas NMDA responses were restricted to a smaller subset and were associated with the absence of A-type K+ currents. In passive astrocytes, approximately half of the cells responded to KA and NMDA. KA responses showed heterogeneous current patterns, including increased cationic conductance and, in a subset of cells, reduced outward K+ currents, whereas NMDA responses were comparatively homogeneous. Discussion: These findings demonstrate substantial functional heterogeneity of ionotropic glutamate receptor responses within established optic nerve glial populations. Glutamate responsiveness does not define distinct glial cell types but rather represents an additional functional feature within NG2 glia and astrocytes. This diversity may enable glial cells to adapt to local neuronal activity and contribute to axon-glia communication and white matter homeostasis.