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Figure 2: Alterations in intracellular signaling cascades affecting postsynaptic AMPAR response in Ts65Dn hippocampus. Green indicates elevated levels/activity at baseline, while red indicated diminished activity. During LTP (right), enhanced CaMKII and GluR1 subunit phosphorylation in Ts65Dn synapses may result in a saturated condition incapable of additional potentiation. Reduced ERK activity may reduce migration of new AMPARs into the PSD. In LTD, overexpression of RCAN1 should reduce the activity of PP2B (calcineurin) resulting in reduced internalization of AMPA receptors and potential reduction of NMDAR mean open times. Rescue of LTD in Ts65Dn mice by NMDAR antagonists suggests enhanced NMDAR activity contributes to altered LTD through yet unidentified mechanisms.