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We have recently shown that human neural stem cell (NSC) grafts ameliorate motor neuron disease in SOD1 transgenic rodents. Here we study structural aspects of integration of neuronally differentiated human NSCs in the motor circuitry of SOD1 G93A rats. Human NSCs were grafted into the lumbar protuberance of 8\u2010week\u2010old SOD1 G93A rats; the results were compared to those on control Sprague\u2010Dawley rats. Using pre\u2010embedding immuno\u2010electron microscopy, we found human synaptophysin (+) terminals contacting the perikarya and proximal dendrites of host \u03b1 motor neurons. Synaptophysin (+) terminals had well\u2010formed synaptic vesicles and were associated with membrane specializations primarily in the form of symmetrical synapses. To analyze the anatomy of motor circuits engaging differentiated NSCs, we injected the retrograde transneuronal tracer Bartha\u2010pseudorabies virus (PRV) or the retrograde marker cholera toxin B (CTB) into the gastrocnemius muscle\/sciatic nerve of SOD1 rats before disease onset and also into control rats. With this tracing, NSC\u2010derived neurons were labeled with PRV but not CTB, a pattern suggesting that PRV entered NSC\u2010derived neurons via transneuronal transfer from host motor neurons but not via direct transport from the host musculature. Our results indicate an advanced degree of structural integration, via functional synapses, of differentiated human NSCs into the segmental motor circuitry of SOD1\u2010G93A rats. J. Comp. Neurol. 514:297\u2013309, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cne.22022","type":"journal-article","created":{"date-parts":[[2009,2,23]],"date-time":"2009-02-23T19:29:33Z","timestamp":1235417373000},"page":"297-309","source":"Crossref","is-referenced-by-count":108,"title":["Human neural stem cell grafts in the spinal cord of SOD1 transgenic rats: Differentiation and structural integration into the segmental motor circuitry"],"prefix":"10.1002","volume":"514","author":[{"given":"Leyan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David 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