A principal function of astrocytes is to monitor local synaptic activity by their expression of metabotropic neurotransmitter receptors for both glutamate and GABA (Parpura and Verkhratsky, 2011; Rusakov et al., 2011). These receptors activate intracellular signaling pathways, mediated primarily by increases in cytosolic Ca2+, which are linked to synaptic plasticity (Parpura and Zorec, 2010). To assess the selective impact of human astrocytes on neural transmission within the host murine neural network, we compared synaptic activity in hippocampal slices prepared from human glial chimeric mice, to that of both their unengrafted and allografted littermate controls. We focused on the hippocampal dentate granule layer, because of the many electrophysiological and behavioral tests by which hippocampal function, learning and LTP could be assessed (Lee and Silva, 2009). In addition, human cells typically densely engrafted this area; these included an admixture of GFAP+/hNuclei+ and NG2+/hNuclei+ cells (Figs. 1B, F, 2G). Stimulation of the medial perforant path (Colino and Malenka, 1993) consistently evoked a significantly steeper slope of field excitatory postsynaptic potentials (fEPSP) in the humanized chimeric mice than in either their uninjected littermates or
