Fig. 2.

Coupled kinase and phosphatase switches can produce tristability. A. Simulation results for coupled switch model. The basal state undergoes LTP in response to high concentration (4 μM for 2 sec) of Ca²⁺. The basal state goes to LTD state in response to moderate Ca²⁺ elevation (2.2 μM for 2 sec). B. Enzyme activities during LTP and LTD. Leftt panel: kinase and phosphatase activities during LTP. K* and P* denote the concentration of active kinase and phosphatase respectively. Before Ca²⁺ stimulation, both kinase and phosphatase are nearly inactive. During high level of Ca²⁺ application, kinase activity is dominant. After Ca²⁺ removal, active kinase represses the phosphatase activity below its initial level (see inset). Right panel: Kinase and phosphatase activities during LTD. Phosphatase is activated by Ca²⁺ pulse of 1 μM for 2sec and stays in the active state after Ca²⁺ is removed. During maintenance of LTD, active phosphatase represses kinase activity (see inset). C. Robustness of basal state to perturbation. Different levels of Ca²⁺ pulses (step size 0.1 μM for 2 sec) are applied on top of basal concentration (0.1 μM) and responses are traced. Basal state is robust to the Ca²⁺ concentration less than or equal to 0.5 μM. Concentrations higher than 0.6 μM evoke LTD (red trace). D. Dependence of sign of synaptic modification on Ca²⁺ level during a pulse (note similarity to BCM curve). E. Reversals of LTP and LTD. The basal state which is robust to small perturbation (the first stimulation: 0.4 μM Ca²⁺ for 2sec) undergoes LTP by the second stimulation (4 μM for 2sec). The third stimulation (2.2 μM for 1.4sec) reverses the potentiated state back to basal level (depotentiation). The fourth (2.2 μM for 2sec) and the fifth (2.93 μM for 2sec) stimulations induce and reverse LTD, respectively (dedepression).