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. 2021 Aug 10;10:e64644. doi: 10.7554/eLife.64644

Figure 7. ppERK favors spaced stimuli in response to calcium input, in contrast to temporal sensitivity of CaMKII.

(A) Time course of ppERK in response to four trains of 100 Hz calcium stimuli (1 μM concentration) shows sustained and prolong ppERK with 3 and 40 s ITI. (B) ppERK AUC changes with PP1 quantity, but still is highest for spaced ITIs. (C) Increasing PP1 quantity or lowering calcium concentration makes CaMKII more sensitive to shorter ITIs.

Figure 7.

Figure 7—figure supplement 1. ppERK temporal sensitivity is similar to that of inactive SynGap.

Figure 7—figure supplement 1.

Normalized activity is the total activity divided by the maximum total activity (over all ITI). Inactive SynGap is the SynGap bound to pCaMKII or dispersed to the dendrite. Active RasGRF is the RasGRF bound to calmodulin. The model is simulated using L-LTP patterns of input. (A, B) Using 1 µM calcium, temporal sensitivity of ppERK is similar to inactive SynGap regardless of PP1 quantity. (C) temporal sensitivity of ppERK is similar to inactive SynGap using alternative CaMKII model (D). Temporal sensitivity of ppERK matches active RasGRF more than inactive SynGap with low calcium concentration. (E). Pearson's R correlation was calculated between ppERK and SynGap or RasGRF. Correlation coefficients (R) demonstrate that the temporal pattern of ppERK is highly correlated with the temporal pattern of inactive SynGap, except with low calcium, in which case it is highly correlated with the temporal pattern of RasGRF.
Figure 7—figure supplement 2. SynGap availability controls the magnitude of ppERK during L-LTP induction.

Figure 7—figure supplement 2.

The model is simulated using L-LTP patterns of input with 1 µM calcium. (A) Blocking dispersion of pSynGap to the dendrite or blocking CaMKII catalytic activity (pCaMKII bound SynGap) reduces ppERK, whereas allowing CaMKII to bind (but not phosphorylate) SynGap (No pCaMKII bound SynGap) enhances total ERK activity. (B) Time course of ppERK produced by calcium pathways at 3 (B1) and 300 (B2) s ITI. ERK activation by SynGap is enhanced and delayed when RasGRF is blocked.