Figure 6.

Cln3 rescue in either astrocytes or neurons reduces epileptiform spikes, but only neuronal rescue fully normalizes network dynamics as measured on EEG

(A) Correction of either astroctyes (FlexCln3/Cln3^{Δex78/Δex78}/Gfap-Cre, blue) or neurons (FlexCln3/Cln3^{Δex78/Δex78}/Syn1-Cre, green) reduced spike burden on EEG in 12-month-old mice. (B–E) Example EEG traces from Cln3^{Δex78/Δex78} (red) and FlexCln3/Cln3^{Δex78/Δex78}/Gfap-Cre motor cortex (blue) show decreased slow delta activity and increased fast activity compared with control motor cortex (black). EEG trace from FlexCln3/Cln3^{Δex78/Δex78}/Syn1-Cre motor cortex (green) shows that rescue of Cln3 expression in neurons normalizes EEG background frequency composition. (F) Power spectral analysis of EEG data recorded in the motor cortex confirm that rescue of Cln3 expression in astrocytes (blue) does not correct disease-associated loss of delta activity, and actually exacerbates increased fast gamma activity. However, correction in neurons (green) normalizes EEG frequency composition. N = 4–5 animals/genotype, after passing a Shapiro-Wilk test of normality, data were analyzed by two-way ANOVA, followed by Sidak’s multiple comparisons test. Significant differences from multiple comparisons testing are shown as ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. Frequency data in (F) in Cln3^WT/Δex78 and Cln3^{Δex78/Δex78} are also shown in Figure 1D.