Stable, long-lasting changes in synaptic function, such as those revealed by our LTP studies, are thought to be involved in learning and memory (Lee and Silva, 2009). Since LTP was markedly enhanced in human glial chimeric mice, we next asked if these mice also exhibited improved learning. We first assessed whether auditory fear conditioning (AFC) - a task in which the mice learn to fear an innocuous tone by pairing it with foot shock (Zhou et al., 2009), and which does not require visual input (rag2-/- mice are blind; Chang et al., 2007) - was potentiated in the human glial chimeras. To this end, we compared the rate of acquisition of AFC by xenografted human glial chimeras to that of both allografted murine glial chimeras, and unengrafted littermate controls (Fig. 6A). The allografted mice – which were also generated in immunodeficient rag2-null hosts - received neonatal grafts of A2B5+/PSA-NCAM- cells isolated from transgenic mice with constitutive EGFP expression, allowing the ready identification of murine donor cells. After just a single pairing of the tone with foot shock, the human glial
