Astrocyte-mediated processes are important for maintaining neuronal homeostasis and proper synaptic transmission. Recent work from the Mandel lab has implicated astrocytes in the X-chromosome linked autism-like spectrum disorder Rett syndrome (RTT), where global mutations in the methyl DNA-binding protein MeCP2 result in dysregulation of neuronal processes and severe mental retardation. Using paired recordings of astrocytes and neurons in cortical slices
(p10-p12) I have shown that stimulation of wild type astrocytes using either depolarization or agonist application leads to potent activation of excitatory signaling in neighboring neurons involving both glutamatergic and GABAergic components. Interestingly, this astrocyte-mediated increase in excitatory neuronal signaling was greatly reduced when astrocyte stimulation was repeated in MeCP2-null mice, a mouse model for RTT. To determine whether this lack of astrocyte-mediated signaling was due to the astrocyte, the neuron, or both cell types being MeCP2 deficient, I took advantage of a MeCP2-GFP knock-in mouse line where female mice have mosaic expression of MeCP2 fused to GFP. The four combinations of paired-recordings between wild type and mutant astrocytes and neurons show that deficits in astrocyte-mediated neuronal signaling occurred when a MeCP2-deficient astrocyte was stimulated regardless of neuronal MeCP2 expression. These results indicate that the expression of MeCP2 in astrocytes is required for astrocyte-mediated modulation of neuronal signaling.