title: Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice.
abstract: Human astrocytes are larger and more complex than those of infraprimate mammals, suggesting that their role in neural processing has expanded with evolution. To assess the cell-autonomous and species-selective properties of human glia, we engrafted human glial progenitor cells (GPCs) into neonatal immunodeficient mice. Upon maturation, the recipient brains exhibited large numbers and high proportions of both human glial progenitors and astrocytes. The engrafted human glia were gap-junction-coupled to host astroglia, yet retained the size and pleomorphism of hominid astroglia, and propagated Ca2+ signals 3-fold faster than their hosts. Long-term potentiation (LTP) was sharply enhanced in the human glial chimeric mice, as was their learning, as assessed by Barnes maze navigation, object-location memory, and both contextual and tone fear conditioning. Mice allografted with murine GPCs showed no enhancement of either LTP or learning. These findings indicate that human glia differentially enhance both activity-dependent plasticity and learning in mice.
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Han
authors.forename: Michael
authors.initials: M
authors.lastname: Chen
authors.forename: Fushun
authors.initials: F
authors.lastname: Wang
authors.forename: Martha
authors.initials: M
authors.lastname: Windrem
authors.forename: Su
authors.initials: S
authors.lastname: Wang
authors.forename: Steven
authors.initials: S
authors.lastname: Shanz
authors.forename: Qiwu
authors.initials: Q
authors.lastname: Xu
authors.forename: Nancy Ann
authors.initials: NA
authors.lastname: Oberheim
authors.forename: Lane
authors.initials: L
authors.lastname: Bekar
authors.forename: Sarah
authors.initials: S
authors.lastname: Betstadt
authors.forename: Alcino J
authors.initials: AJ
authors.lastname: Silva
authors.forename: Takahiro
authors.initials: T
authors.lastname: Takano
authors.forename: Steven A
authors.initials: SA
authors.lastname: Goldman
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001921:Brain; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007858:Learning / Q000502:physiology*; D051379:Mice; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D016548:Prosencephalon / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
chemical_list: D002118:Calcium