The striking population of the recipient mouse brains by human glia raised the possibility that the engrafted human cells might significantly modulate information processing within the host murine neural networks. Indeed, the basal level of excitatory synaptic transmission was increased over a wide range of stimulation intensities. The presence of human glia also enhanced long-term potentiation in human glial-chimeric hippocampal slices, relative to mice that had received conspecific murine glial progenitors or vehicle injection (Fig. 4). Our analysis showed that TNFα was significantly elevated in the human glial chimeric brains, consistent with the potentiation of AMPA receptor-mediated currents (Beattie et al., 2002; Stellwagen and Malenka, 2006). Additional analysis suggested that TNFα may have directly facilitated insertion of the GluR1 subunit to the plasma membrane (Hu et al., 2007), perhaps via its increased phosphorylation at Ser831. TNFα might also potentiate astrocytic glutamate release (Ni and Parpura, 2009; Parpura and Zorec, 2010), which in turn could increase GluR1 subunit phosphorylation by NMDA receptor-mediated activation of PKC (Fig. 5) (Malinow and Malenka, 2002). These pathways might both have contributed to the enhancement of
