To evaluate the electrophysiological properties of human astrocytes engrafted in mice, acute hippocampal slices were prepared from chimeric mice ranging from 4-10 months of age (6.5 ± 0.4 months–old, mean ± SD). Donor astrocytes could be readily identified by their EGFP fluorescence, and by their large, symmetric, highly branched astrocytic morphologies. The tagged donor cells were filled with Alexa 594 or the Ca2+ indicator rhod2 during whole-cell recordings, and their phenotype verified by immunolabeling for GFAP (Fig. 3A). EGFP+ human astrocytes exhibited a higher input resistance than that of host murine astrocytes (51.6 ± 2.5 MΩ, n=37, vs. 29.2 ± 3.2 MΩ, n=17, respectively, means ± SEM; p<0.05, Steel-Dwass test). In contrast, the resting membrane potential of human astrocytes (-69.2 ± 1.5mV, n=37) was not significantly different from that of untagged host astrocytes (-73.9 ± 1.7 mV; n=17; p>0.05) (Figs. 3B-D). Whereas all large and symmetric EGFP+ donor cells exhibited passive membrane currents and linear current to voltage (I/V) curves, another population of smaller EGFP+ human cells with compact, asymmetrically branched morphologies manifested a much higher input resistance (147.8 ±
