Figure 2.

Schematic of the principal pathways implicated by this study in conventional LTD and in LTD facilitated by soluble Aβ oligomers (left panel). Conventional LTD requires NMDAR-mediated influx of extracellular calcium and liberation of intracellular calcium stores. This ultimately activates PP2B, GSK-3b, or p38 MAPK signaling pathways that induce LTD. (Right panel) Soluble Aβ oligomers lead to activation of more NMDAR, leading to extracellular calcium influx and activation of PP2B and GSK-3b pathways to facilitate LTD. Our data suggest that Aβ oligomers decrease glutamate uptake by neuronal transporters (red ×’s), resulting in the enhanced activation of NMDARs and thus facilitation of LTD-inducing pathways.