Fig. 6: PF GABAergic neurons bidirectionally regulate the severity of epileptic seizures.

a, g Schematic of experiment for viral injection and photostimulation in the PF of Vgat-Arch^PF (a) and Vgat-ChR2^PF (g) mice. b, h Representative images of the PF from Vgat-Arch^PF (b) mouse showing the expression of Arch-GFP or Vgat-ChR2^PF (h) mouse showing the expression of ChR2-mCherry. Scale bar, 50 μm. c, i Representative peri-event raster histograms showing the firing rate of a PF GABAergic neuron in response to yellow-light and blue-light stimulation in a Vgat-Arch^PF (c) or Vgat-ChR2^PF (i) mouse. d–f Effects of optogenetic inhibition of PF GABAergic neurons on the development of seizure stage (d), afterdischarge duration (ADD, e), and number of stimulations needed to reach each seizure stage (f) in hippocampal kindling model. Align-and-rank data for a nonparametric ANOVA was used for d, general linear model with repeated measures was used for e, and Mann–Whitney U-test was used for f; **P < 0.01, ***P < 0.001 compared with blue-light control. j–l Effects of optogenetic activation of PF GABAergic neurons on the development of seizure stage (j), ADD (k), and number of stimulations needed to reach each seizure stage (l) in the hippocampal kindling model, in the presence of GABA_A receptor antagonist bicuculline (Bic, intra-PF injection). Align-and-rank data for a nonparametric ANOVA with post-hoc Dunn’s test for multiple comparisons was used in j, general linear model with post-hoc Dunn’s test for multiple comparisons was used in k, and an Kruskal–Wallis test with post-hoc Dunn’s test for multiple comparisons was used in l; *P < 0.05, **P < 0.01 compared with yellow-light control and ^#P < 0.05, ^##P < 0.01 compared with blue-light with bicuculline. m Representative image of the PF from a Vgat-hM3Dq^PF mouse. Scale bar, 100 μm. n–q Effects of chemogenetic activation of PF GABAergic neurons on the latency to generalized seizure (GS, n), the number of focal seizures (FSs, o) and GSs (p), and mortality (q) in KA-induced acute seizure model. Mann–Whitney U-test, *P < 0.05 compared with saline. The number of mice used in each group is indicated in the figure. Data are presented as means ± SEM. Source data are provided as a Source Data file.