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

Figure 6. ppERK favors spaced stimuli in response to cAMP input.

(A) Time course of ppERK in response to 4 trains of 100 Hz stimuli of cAMP (Epac, PKA, Giβγ pathways). ppERK peak amplitude decreases with ITI, but the AUC increases with ITI. (B) Total kinase activity in response to cAMP shows that ppERK exhibits sublinear response to cAMP stimuli: the sum (dashed line) is higher than ppERK in response to combination (solid black line). PKA and ppERK have similar temporal sensitivity, favoring spaced stimuli. Two-way ANCOVA (analysis of covariance) of ppERK AUC versus stimulation characteristics (ITI) and type (combination versus summation) as factors (N = 5 in each group) is significant for both stimulation ITI and type (F (2,47) = 42.25, T < 0.0001; T(ITI) = 4.67, P(ITI) < 0.0001, T(type) = 7.92, P(type) < 0.0001).

Figure 6.

Figure 6—figure supplement 1. Uniform ppERK temporal sensitivity within cAMP pathways.

Figure 6—figure supplement 1.

(A) The model is stimulated using L-LTP patterns of input with only a single cAMP pathway active, either Epac, PKA, or Giβγ. Total ppERK versus ITI follows a similar pattern for all pathways, though Epac contributes more, especially for short intertrain intervals. (B) Time courses of cAMP pathways at 3 (B1) and 300 (B2) s ITI. Epac pathway contributes more to ppERK with 3 s (short) ITI, while PKA contributes more with 300 s (spaced) ITI.