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Chunk #23 — RESULTS — Enhanced learning in humanized chimeric mice

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Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice.
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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 chimeric mice exhibited a significant enhancement in learning of the tone foot shock association: They showed greater fear to the tone as measured by scoring freezing behavior (the cessation of all movement except for respiration), than did either allografted chimeras or unengrafted controls (n = 5-20; 9.6 ± 1.0 months-old; F = 18.9, two-way repeated measures ANOVA; p < 0.001). Moreover, after 3 continuous days of training humanized chimeric mice also showed enhanced AFC during the 3 remaining days of testing, as manifested by their higher levels of freezing in response to the conditioned tone (p<0.01, post hoc Bonferroni test). In contrast, neither murine glial chimeric mice nor unengrafted controls manifested any increase in freezing behavior during the same period, despite having been subjected to an identical fear conditioning paradigm (p>0.05; Bonferroni test) (Fig. 6A). Of note, no differences were observed in the reaction to foot shock between the human glial chimeras and their controls (n=5, 9.6 ± 1.0 months