Figure 4. Synaptic cooperativity is strongest for synaptic inputs located on the same dendritic branch.

(A) Schematic indicates spatiotemporally distributed inputs to one, two, four, or eight dendritic branches (legend colors also correspond to (B) and (C). (B) Peak spine calcium for all stimulated spines is shown as a box and whisker plot with outliers for various patterns of spatiotemporally distributed inputs. Eight, 16, 24, or 32 spines per branch are stimulated with one, two, four, or eight total branches being stimulated for 0, 2.5, 5, or 10 ms mean interstimulus interval per branch (panels left to right). Stimulating multiple branches with the same number of spines/branch does not strongly affect spine calcium elevation (e.g. green arrowhead, eight spines per branch on two to eight branches with 0.0 ISI), indicating branch independence. However, near threshold (e.g. purple arrowhead, 16 spines/branch on two versus four branches for 0.0 ms ISI), stimulating multiple branches enhances spine calcium elevation, indicating small branch interactions whereby inputs to other branches can reduce the threshold of required inputs on a branch for supralinear spine calcium elevation. Spine calcium elevation decreases with increasing ISI (i.e. decreased peak calcium in panels from left to right), indicating that cooperation among synaptic inputs is limited to a temporal window of 10 s of ms. Note that for temporally distributed simulations, the ISIs are exponentially distributed with the average value indicated. The average ISI per branch means (for example) that an average ISI of 10 ms per branch corresponds to a total average ISI of 5 ms for all inputs when two branches are stimulated, and 2.5 ms for all inputs when four total branches are stimulated. The order of inputs was randomly applied and followed no spatial pattern. (C) Soma membrane potential corresponding to spine calcium concentration measures in (B). Plateau potential duration corresponds to spine calcium supralinearity. Action potentials are clipped in voltage traces. In some cases (e.g. orange arrowhead), increasing ISI from 0 to 2.5 ms enhances cooperativity among synaptic inputs, as it prolongs the duration of the plateau potential.