Fig. 3: BARNI channel activation decreases the frequency of spontaneous seizures.

a Experimental setup. Mice received unilateral dorsal intrahippocampal kainic acid (IHKA) injections. After at least 3 weeks for the development of chronic spontaneous seizures, mice received bilateral hippocampal injection of AAV virus encoding either BARNI or a Scramble control vector and implanted with EEG recording electrodes. b Representative EEG traces observed in mice expressing BARNI or Scramble control vector at baseline and after a single i.p. injection of bradanicline. Scale: 0.4 V, 40 s. c Frequency of spontaneous seizures decreased after a single i.p. injection of bradanicline (Br). 30-min bins, values normalized to seizure frequency observed one hour before treatment for each mouse (F(33, 374) = 2.137, P = 0.004, two-way RM ANOVA, Time × Vector + Drug). d Representative time course of detected seizures in Scramble and BARNI expressing mice after either vehicle (Veh) or bradanicline (Br) i.p. injection. e Brief change in the duration of spontaneous seizures observed after a single i.p. injection of bradanicline. 30-min bins, values normalized to seizure duration observed one hour before treatment for each mouse (F(33, 374) = 3.239, P < 0.0001, two-way RM ANOVA, Time × Vector + Drug). Significance values on graphs are shown for comparison between vehicle and bradanicline treatment in BARNI-expressing mice at each time point using paired t-test. Significance values in legend are shown for comparison between vector expression and treatment groups using two-sided Tukey’s multiple comparisons tests. Mean ± SEM, n = 9 Scramble, 10 BARNI mice. *P < 0.05, ***P < 0.001, ****P < 0.0001. Exact P-values are in Supplementary Table 1. Source data are provided as a Source Data file.