Figure 11.

Model for astrocyte-mediated regulation of neuronal NMDARs. (A) When hippocampal neurons are cultured in the absence of glia, glutamate released from the presynaptic terminal activates both GluN2A and GluN2B NMDARs localized at synapses. (B) In the presence of glia, astrocytes secrete a currently unidentified soluble factor or factors (blue arrow) that activate PKC. Through phosphorylation of either the GluN2B subunit itself (solid green arrow) or, more likely, an ancillary protein (X) associated with the NMDAR signaling complex (dashed red arrows), PKC activation leads to an increase in the activity of synaptic GluN2B NMDARs without affecting the activity of either synaptic GluN2A NMDARs or extrasynaptic GluN2B NMDARs; it remains to be seen whether astrocytic modulation is specific for GluN1/2B heterodimers or it also affects GluN1/2A/2B heterotrimers (as shown).