Mechanism for the emergence of input-order constraint.

<p>(A) Active CaMKII and PP1 traces for different Δt values. The vertical red and green dotted lines mark the start of calcium and dopamine inputs, respectively. The CaMKII and PP1 levels are normalized by the maximum values observed with calcium input alone, i.e. without any dopamine input. Each panel mentions the associated Δt value. The upper panels have the same x-axis values as the lower panels. (B) The amplitude of active CaMKII as a function of Δt with or without ARPP-21 in the modeled system. The y-axis is normalized by the amplitude of CaMKII produced by the calcium input alone. (C) Traces for ARPP-21 phosphorylation (pARPP-21), pARPP-21 sequestration of Ca²⁺/calmodulin (pARPP-21*CaMCa4) and Ca²⁺/calmodulin available for CaMKII activation (Available CaMCa4) for three different Δt, (C1) Δt = -2s, (C2) Δt = -1s and (C3) Δt = 1s. The left figure panels show pARPP-21 and pARPP-21*CaMCa4 whereas the right panels show available CaMCa4. The vertical red and green dotted lines mark the start of calcium and dopamine inputs, respectively. pARPP-21 and pARPP-21*CaMCa4 are normalized to the maximum level of total phosphorylated ARPP-21. The available CaMCa4 is normalized by the maximum available CaMCa4 with calcium input alone. (D) Timecourse of ARPP-21 phosphorylation for different values of Δt. The vertical green dotted line marks the start of dopamine input. The start time of calcium input depends on the value of Δt relative to the start time of dopamine input. The y-axis is normalized by the basal level of phospho-ARPP-21.