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. 2015 Jul;22(7):344–353. doi: 10.1101/lm.038844.115

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© 2015 Jalil et al.; Published by Cold Spring Harbor Laboratory Press

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Figure 4. — Two independent feedback loops, each of which can sustain bistability, can combine to give multistability. (A) Evolution in time with two 15-min long elevations of aPKC synthesis (red arrows) starting from low total kinase, K_T, elicited three persistent states: L-LTP (gray dashed), basal (blue dashed), and L-LTD (cyan dashed). Simulated ZIP could both reverse L-LTP and induce L-LTD, depending on the initial concentration as well as on the concentration and duration. (B) Bifurcation diagram with respect to autophosphorylation rate, ɛ, shows this tristability is robust to ∼20% variation (shaded yellow) in the autophophorylation parameter. Solid lines are stable equilibriums resistant to changes in time; dashed lines are unstable equilibriums or thresholds.