Figure 6.

Activity-dependent Ca²⁺/calmodulin (CaM)-dependent protein kinase II (CaMKII) accumulation at the postsynaptic density (PSD) and its actions require binding of CaMKII to N-methyl-d-aspartate receptors (NMDARs). A–C: chemical long-term potentiation (chemLTP) induction results in persistent accumulation of CaMKIIα at the PSD. A and B: electron micrographs of hippocampal synapses labeled for CaMKIIα under control conditions (A) and 1 h after induction of chemLTP (B). Silver-enhanced gold particles appear as irregular black grains. Asterisks indicate grains counted as PSD-associated CaMKII labeling. Scale bar, 100 nm. C: cumulative distribution of densities of gold label for CaMKIIα at individual PSDs from slice cultures under control conditions (filled triangles) and after induction of chemical LTP (filled circles) (217). D: constitutively active CaMKII (T286D-T305A/T306A) (CA CaMKII) in 2-amino-5-phosphonopentanoic acid (APV) (n = 8 pairs) potentiates synapses. E: CA CaMKII containing the I205K mutation (n = 15 pairs) fails to potentiate synapses. Filled circles indicate mean ± SE. F: bar graph of ratios normalized to control (%) summarizing the mean ± SE of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) excitatory postsynaptic currents (EPSCs) of values represented in D and E [Mann-Whitney test (***P < 0.0001)]. G: cells in which CaMKII has been replaced with CaMKII containing the I205K mutation fail to express LTP. Black filled circles represent control cells, green filled circles represent cells expressing the I205K mutation, and gray filled circles represents experiments carried out in APV (121). D–F modified from Ref. 121, with permission from Nature Communications.