Figure 7.

Detrimental effects of large fluctuations of PKC activity during LTD occurrence. Fluctuations in PKC activation are detrimental for the activation of the signaling network if they happen with high peak-to-peak amplitude fluctuations or with high frequency. Single runs of the model using equal seeds to initiate the simulations illustrate this detrimental effect. Each column (A, B) shows the results of simulations using the same seed. In these examples, a Ca²⁺ pulse of 4 s and peak concentration of 3.5 μmol.L⁻¹ applied at 10 min was used to induce the activation of the signaling network, and two (A) or six (B) transient perturbations (indicated by arrows) reducing PKC activity to a level varying from 80% to 0% of its activation (top to bottom) were applied. Each perturbation had a duration of 3 s. Both larger amplitude and high-frequency fluctuations in PKC activity negatively interfere with the activation of the signaling network, leading to failure of LTD (indicated by asterisks in the panel).