(a) Six spines at 0.5-μm intervals were added to the modelled neuron with a small soma and a straight dendrite with segments of decreasing diameter from the primary to the tertiary dendrite (as in c top). Spines are all identical: spherical spine head (r=0.5 μm) and cylindrical spine neck (r=0.25 μm, L=1 μm). cAMP was released in the shaft or spine heads as indicated. (b) Areas under the curve of nuclear pT34-DARPP-32 time course following the release of cAMP at nine dendritic locations as a function of the distance to soma. The model was not run for release sites <40 μm to soma since this region does not include spines in MSNs. (c–e) Effects of spines density on the synapse-to-nucleus signalling. (c) Modelled neurons with no spines (top), 10 spines (middle) or 51 spines (bottom). (d) Corresponding integrated activities (areas under the curve of time courses) of nuclear pT34-DARPP-32. (e) Same plots as in d normalized to the response in the absence of spine. The y axis scale is expanded to emphasize small differences. In e and d the grey shading intensity indicates spine density as reported in ref. 31. (f–h) Seven additional dendrites were modelled as truncated cylinders with the diameter of a primary dendrite, in which when molecules diffuse, they disappear (f, ‘holes’). Nuclear integrated activities, following cAMP release at nine dendritic locations in a neuron with one primary dendrite (as in Fig. 3e, black) or with seven additional dendrites (red) (g). Same red plot as in g with a different scale of y axis. (i,j) Striatal neuron modelled with three unbranched primary dendrites of decreasing segmental diameter. cAMP was released at nine different dendritic locations (as in Fig. 2b) either in one of the three dendrites (1 release site, blue) or at three identical sites in the three dendrites (3 release sites, red) (i). Nuclear integrated activities (j), following cAMP release at nine dendritic locations in a neuron with three primary dendrites. In f–i, the diameter of the secondary and tertiary dendrites was increased as compared to the initial values to mimic the presence of spines.