AMPAR Synaptic Membrane Localisation and Conductance in Response to Sustained Inputs

<div><p>Each panel is computed from a series of steady-state calculations where the activity of the selected input pathway was scaled with respect to its basal activity. The <i>x</i>-axis is this scaling ratio. The conductance is calculated as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0010020#pcbi-0010020-g003" target="_blank">Figure 3</a> and is expressed as the secondary <i>y</i>-axis, as a percentage of maximal conductance (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0010020#s4" target="_blank">Materials and Methods</a>).</p><p>(A) Changing activity of CaMKII leads to small changes in synaptic membrane localisation of AMPARs, but phosphorylation of GluR1 on Ser831 gives a doubling of synaptic conductance when CaMKII activity is scaled above basal levels.</p><p>(B) Low concentrations of PKA result in reduced exocytosis of AMPAR. Basal concentrations of PKA (ratio ~ 1) are required to localise AMPAR to the synaptic membrane, and higher concentrations cause a conductance increase. This occurs because of phosphatase saturation leading indirectly to a rise in Ser831 phosphorylation due to CaMKII. The net effect is that changes in PKA activity can lead to a large change in AMPAR conductance in either direction.</p><p>(C) Changes in PP1 concentrations have little effect on AMPAR localisation. However, low PP1 leads to high phosphorylation of GluR1-Ser831 by CaMKII, and hence high conductance.</p><p>(D) Lower rates of receptor recycling to the internal pool lead to a small increase in synaptic membrane localisation. High rates bring most of the receptor to the internal pool.</p>