Figure 5.

Ca²⁺/calmodulin (CaM)-dependent protein kinase II (CaMKII) is required and sufficient for long-term potentiation (LTP). A and B: inhibition of CaMKII blocks LTP. Effect of intracellular application of the CaM-binding peptide (CBP) on LTP. A: the magnitude of the initial excitatory postsynaptic potential (EPSP) slope in populations of cells recorded with microelectrodes containing 1.1 mM CBP (190 µM: n = 11) (open triangles) or the control peptide CTP₂ (190 µM: n = 8) (filled triangles). B: the initial slope field EPSP slope recorded in the 2 populations of slices demonstrating that the LTP was essentially identical in the 2 populations (197). C: extracellular monitoring shows LTP after tetanic stimulation. D: simultaneous monitoring of synaptic potentials with intracellular electrode containing 1.1 mM CaMKII(273–302) shows no persistent potentiation after tetanic conditioning. E: transmission in a nontetanized pathway, monitored with the CaMKII(273–302)-containing electrode, is constant throughout the experiment. Error bars indicate SE for representative individual time points. Insets: average of 10 consecutive potentials obtained at the times indicated on time axis. Scale bars, 0.33 mV, 12.5 ms (C); 5.0 mV, 12.5 ms (D) (198). F and G: constitutively active CaMKII mimics LTP. F: diagram showing the recording setup. Two independent pathways are stimulated. In one pathway a saturating level of LTP had been induce. The other pathway serves as a control. G: at time 0 a whole cell recording is made with a patch electrode containing constitutively active CaMKII (truncated). The control pathway shows a robust enhancement, whereas the pathway expressing saturating LTP shows little enhancement (199). Images modified from Refs. 197–199, with permission from Nature, Science, and Proceedings of the National Academy of Sciences USA, respectively.