We next asked if human astrocytes might affect synaptic plasticity, by assessing the effect of human glia on long-term potentiation (LTP). Two trains of high frequency stimulation (HFS) potentiated the fEPSP slope to 151.2 ± 8.1% of baseline in chimeric mice, compared with 138.6 ± 7.6% in control littermates (n = 7 mice in both groups; 13.8 ± 1.1 vs. 12.6 ± 0.4 months-old, respectively; ages provided as mean ± SEM) (Fig. 4B). The enhancement of fEPSP slope persisted at 60 min in humanized chimeric mice (113.6 ± 3.8 %, p < 0.05), whereas fEPSP slope in unengrafted controls fell to 103.2 ± 3.9 % (not significantly different from the fEPSP slope prior to HFS; p=0.169). Mouse allografted controls exhibited an initial increase to 138.5 ± 2.3%, which fell to 103.8 ± 1.3 % at 60 min (not significantly different from the fEPSP slope prior to HFS; n = 7, 14.0 ± 0.1 months-old; p = 0.29, t test) (Fig. 4B). Thus, the observed enhancement of LTP was a specific feature of human glial chimerization, and were not attributable to cell engraftment per se.
