Signaling models for dopamine-dependent temporal contiguity in striatal synaptic plasticity
Fig 5
Smallness of spines was important for short-term PKA activity and its time window.
(A) Domain size affects cAMP dynamics. Spines/thin dendrites are small (radius r = ~0.1 μm), thus having small cytosolic volumes per membrane area (top). The membrane AC1 activity rapidly increases cytosolic cAMP level (the number density of black points), which is rapidly decreased by the membrane PDE. In the somas, cAMP level is increased by the membrane AC5, and slowly decreased by the membrane PDE (bottom). The cAMP levels (the number density of black points per cytosolic volume) are detected by PKA. (B) PKA activities (AKAR2-CR) in the spines and somas in the experiment [4]. Here, DA denotes DA burst, AP designates postsynaptic burst, and papaverine is a PDE inhibitor. The data were taken from the experiment by Yagishita et al. [4]. (C) The simulated PKA activity dynamics with (red dotted lines) and without (black lines) an 80% decrease in PDE. (D–G) Small domain size is necessary for the short time window for PKA activity. (D) A spherical domain with the radius (r). In this domain, pre–post pairing activated VGCCs and NMDARs, increasing cytosolic Ca2+ level for AC1 activation, while DA burst activated AC1 via membrane Golf. (E) Time windows for the PKA activity in the domain with the indicated radiuses r. (F) Ca2+ dynamics with the radiuses r indicated in (E). (G) Radius dependence of FWHMs of the time windows. The FWHMs under a fixed Ca2+ dynamics (same in the case of r = 0.1 μm) were also plotted (dashed line).