The unique processing capabilities of the human brain reflect a number of evolutionary adaptations by its cellular constituents. One especially distinct feature of the adult human brain's cellular composition is the size and complexity of its astrocytic cohort.

Human astrocytes are both morphologically and functionally distinct from those of infraprimate mammals, in that human astroglia are larger and exhibit far greater architectural complexity and cellular pleomorphism, as well as more rapid syncytial calcium signaling, than their murine counterparts. These phylogenetic differences are of particular interest, since astrocytes can both coordinate and modulate neural signal transmission. These observations promise to fundamentally transform our view of astrocytes, since current concepts of the role of astrocytes in neural network performance are based almost entirely on studies of astrocytic physiology in the rodent brain.

To assess the cell-autonomous and species- selective properties of human glia, human glial progenitor cells (GPCs) were engrafted 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.

Keywords: transplantation, fetal tissue, astrocytes, astroglia.