Fig. 1: Subicular pyramidal neurons control the generalization of hippocampal seizures.
From: Discrete subicular circuits control generalization of hippocampal seizures
a Top, scheme of experiments for Ca2+ fiber photometry of subicular pyramidal neuron during hippocampal seizures. Bottom, GCaMP6(s) expression in the subiculum (SUB), and overlap with CaMKII+. Scale bar, 25 μm. b Left, typical EEG and average calcium signals (ΔF/F) during focal seizures (FSs). Right, corresponding heatmap, each row represents one trial. c Left, typical EEG and average calcium signals during secondary generalized seizure (sGSs). Right, corresponding heatmap, each row represents one trial. Representative images (d) and quantification (e) of c-Fos activation pattern in the subiculum in mice with no seizure (Sham), FS, and sGS. Scale bar, 100 μm. One-way ANOVA with post hoc Dunnett’s test, *P < 0.05, ****P < 0.0001 compared with Sham. f Overlap between activated c-Fos and CaMKII+ neurons after sGSs and quantification. Scale bar, 25 μm g Quantification of c-Fos in distal, proximal, deep, and superficial areas of the subiculum after sGSs. Paired t-test, *P < 0.05. h Scheme of optogenetic experiments in sGS acquisition. i Effects of optogenetic modulation of subicular pyramidal neurons on the development of seizure stage and after-discharge durations (ADD). Two-way repeated measures ANOVA with post hoc Scheffe’s test, *P < 0.05 compared to eGFP. j, k Number of stimulations needed to reach FS (j) and sGS (k) during seizure development. One-way ANOVA with post hoc Dunnett’s test, *P < 0.05, **P < 0.01. l Typical sGS EEGs recorded from the CA3. m Scheme of optogenetic experiments in sGS expression. Effects of optogenetic activation of subicular pyramidal neurons on seizure stage (n), ADD (o), and sGS durations (GSD, p) during sGS expression. One-way repeated measures ANOVA with post hoc Dunnett’s test, *P < 0.05 compared to Pre, #P < 0.05 compared to Post. Effects of optogenetic hyperpolarization of subicular pyramidal neurons on seizure stage (q), ADD (r), and GSD (s) during sGS expression. One-way repeated measures ANOVA with post hoc Dunnett’s test, **P < 0.01 compared to Pre, ##P < 0.01 compared to Post. The number of mice used in each group is indicated in the figure. Data are presented as means ± SEM.
