(A and B) Raster plots reveal that PP stimulation results in moderate excitation of both WT and CLN3–/– stratum radiatum of the hilus, CA3, and CA1 at 2 months of age. (C) Permutation sampling analysis at 2 months demonstrates minimal differences in excitability between WT and CLN3–/–. Pixels with P > 0.05 are masked in gray. For regions of significance with P < 0.05, the difference in fluorescence change (ΔF/FWT – ΔF/FCLN3KO) is shown. Cooler colors indicate relative hypoexcitability of the CLN3–/– CA proper. (D–F) At 6–7 months and (G–I) 18–21 months of age, there is progressive hypoexcitability throughout the CA proper. (J) Quantification of total fluorescence change in the hilus and CA3 regions supports hypoexcitability in CLN3–/– mice at 6 and 18 months. (K) The CA1 region demonstrates a significant decrease in excitability by 18 months. (J and K, 2-way ANOVA, followed by Tukey’s multiple-comparisons test). For all panels: *P < 0.05. Group sizes (n = slices, N = mice): 2-month WT n = 24, N = 6; 2-month CLN3–/–
n = 26, N = 5; 6- to 7-month WT n = 23, N = 5; 6- to 7-month CLN3–/–
n = 30, N = 8; 18- to 21-month WT n = 25, N = 7; 18- to 21-month CLN3 n = 26, N = 7. For all graphs mean ± SEM shown.