To specifically assess hippocampus-dependent learning, we next prepared chimeric mice using rag1 immunodeficient mice (maintained on a C57/Bl6 background), which differ from their rag2-null counterparts (on a C3H background) by having normal vision. We first compared the net engraftment of human GPCs, as well as their relative differentiation into hNG2+ GPCs or GFAP+ astroglia, in human glial chimeras established in rag1-null and rag2-null mice. We focused on hippocampal learning, as this region was used for our analysis of LTP (Lee and Silva, 2009; Manns and Eichenbaum, 2009). We found that both the engraftment and differentiation of human GPCs in rag1- and rag2-immunodeficient mice were indistinguishable from one another (Fig. S5B-C). On that basis, we next assessed the effect of chimerization of rag1-null immunodeficient mice on contextual fear conditioning (CFC), a hippocampal-dependent task in which mice learn to fear a context in which they receive a foot shock (Fanselow and Poulos, 2005). The human glial-chimeric mice exhibited enhanced performance in CFC throughout all 4 days of training (Fig. 6B). By just the second day, the human glial-chimeric mice exhibited substantially more
