Several mechanisms exist by which astrocytes can modulate excitatory transmission. Astrocytes release ATP, which after degradation to adenosine by extracellular ectonucleotidases, can suppress both basal synaptic transmission, and activity-dependent increases in synaptic strength (Pascual et al., 2005; Zhang et al., 2003). However, it seems unlikely that adenosine contributed to the enhanced synaptic strength observed in the xenografted mice. The A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (Grover and Teyler, 1993; Wu and Saggau, 1994) did not decrease the threshold for induction of LTP in control mice; in slices exposed to 100 nM DPCPX, the fEPSP slope returned to 101.9 ± 3.6% 60 min after HFS, similar to untreated slices (Figs. 4D-E). Thus, it is unlikely that the reduced threshold for LTP in chimeric mice was a consequence of altered adenosine concentrations.
