Nested Bistability for Weakly Coupled Switches

<div><p>(A) Schematic of independent PSD-localised PP1 enzyme activities for CaMKII and AMPAR. The two PP1 activities are labelled PP1-PSD-CaMKII and PP1-PSD-AMPAR, respectively. The asterisks represent phosphorylation.</p><p>(B) Time course of system response to Ca²⁺ (2.7 μM, 500-s duration), then cAMP (0.108 μM, 2,000-s duration) stimulus. The initial activation of CaMKII leads to a slow turn on of the AMPAR system.</p><p>(C) Time course of system response to cAMP (0.108 μM, 2,000-s duration), then Ca²⁺ (2.7 μM, 500-s duration) stimulus. First the AMPAR system turns on, then, following the Ca²⁺ stimulus, the CaMKII turns on. The conductance of the synapse has different levels in each of these states.</p><p>(D) Stochastic run for 60 h, showing resting, AMPAR only, and AMPAR + CaMKII activity states.</p>