Fig. 4: Selective loss of off-hotspot calcium potentiation in SK2 KO but not CaMKII TT305/6 VA mice underlines the spatial role of intrinsic plasticity in global amplification.

a Schematic diagram illustrating the linescan of PC dendrite calcium signals (blue) in response to PF stimulation. b–d Conceptual models depicting hypothesized fluorescence signals along the PC dendrites of (a). Dark and light traces showing pre- and (early) post-tetanus data, respectively. The X-axis represents the ΔF/F normalized by the maximum value of pre-tetanus data. e–g Representative two-photon images of individual PCs from each genotype are shown in the left panels, with corresponding linescan fluorescence signals in the right panels. Blue shaded areas depict the linescan recording site. The dark and light traces represent pre- and post-tetanus data. The hotspot area (pixels with >0.9 normalized pre-tetanus ΔF/F) expanded from a length of (B) during the pre-tetanus period to a combined length of (A) + (B) + (C) during the post-tetanus period, thus the (A) + (C) represents Δlengths. Scale bar is 50 μm. h–j The top panel displays the cumulative lengths as a function of fluorescence level, while the bottom panel displays the corresponding Δlengths of the representative data shown in (e–g). Cumulative lengths were obtained by summing up the dendritic length exhibiting the given fluorescence level, depicted as the dashed lines in (e) and the top (h). Δlengths were calculated by subtracting post-tetanus from pre-tetanus cumulative length, as indicated by the dashed lines in (h). k–m For all cells from all mice in each group, mean ± SEM of cumulative lengths (top panel) and Δlengths (bottom panel) as in (h–j). n Superimposed genotype Δlengths obtained from the bottom (k–m). The horizontal bar represents the median ± median absolute deviation of the distribution. Asterisks denote significance in distribution shift using Dunn & Sidák’s approach (*p < 0.05; **p < 0.01; ***p < 0.001) following Kruskal–Wallis test (H[2] = 161.17, p < 0.001, n = 3929). o, p Mean ± SEM of Δlengths, calculated from the off-hotspot (o) and hotspot (p) grey shaded areas shown in (n), with individual cell values alongside. (One-way ANOVA: off-hotspot, F[2, 153] = 3.9, p = 0.022; hotspot, F[2,153] = 12.45, p < 0.001, n = 624). Asterisks denote the significance levels of post hoc comparisons using Tukey’s HSD (*p < 0.05; **p < 0.01; ***p < 0.001). LTP long-term potentiation. IP intrinsic plasticity.