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. Author manuscript; available in PMC: 2013 Sep 6.

Published in final edited form as: Neuroscience. 2012 May 18;219:33–47. doi: 10.1016/j.neuroscience.2012.05.003

Thalamic inhibition of mTOR or KCC2 increases seizure susceptibility to pilocarpine. (A–C) Rapamycin or vehicle was delivered bilaterally to the thalamus or GP via microinjection twice per day for three days prior to i.p. administration of pilocarpine. Rats that received rapamycin via thalamic injection showed a significant increase in average seizure duration (Veh/thalamus: 1.29 ± 0.59, Rap/thalamus: 7.02 ± 2.74 and Rap/GP 0.82 ± 0.39) (A), average seizure scale (Veh/thalamus: 1.06 ± 0.43, Rap/thalamus: 2.56 ± 0.41 and Rap/GP 0.64 ± 0.27) (B), and average number of stage 4 and 5 seizures (Veh/thalamus: 0.83 ± 0.41, Rap/thalamus: 4.25 ± 1.76 and Rap/GP 0.44 ± 0.29) (C) (ANOVA with Tukey post hoc adjustment; mean ± SEM; * indicates p<0.05; n=8–9). (D–F) Systemic administration of the KCC2 blocker furosemide (40 mg/kg) via i.p. injection 15 min prior to pilocarpine i.p. injection. Rats treated with furosemide showed a significant increase in seizure duration (control: 0.73 ± 0.16 vs furosemide: 5.17 ± 1.17) (D), average seizure scale (control: 1.03 ± 0.16 vs furosemide: 2.48 ± 0.30) (E), and average number of stage 4 and 5 seizures (control: 0.90 ± 0.23 vs furosemide: 3.13 ± 0.40) (F). (G–I) Furosemide or vehicle was delivered bilaterally to the thalamus via microinfusion 15 min prior to i.p. administration of pilocarpine. Rats treated with furosemide locally showed a significant increase in average seizure duration (control: 0.41 ± 0.27 vs furosemide: 4.54 ± 1.84) (G), average seizure scale (control: 0.52 ± 0.30 vs furosemide: 2.25 ± 0.56) (H), and average number of stage 4 and 5 seizures (control: 0.18 ± 0.18 vs furosemide: 3.36 ± 1.36) (I). (mean ± SEM; * indicates p<0.05; t-test; n=6–11).

Thalamic inhibition of mTOR or KCC2 increases seizure susceptibility to pilocarpine. (A–C) Rapamycin or vehicle was delivered bilaterally to the thalamus or GP via microinjection twice per day for three days prior to i.p. administration of pilocarpine. Rats that received rapamycin via thalamic injection showed a significant increase in average seizure duration (Veh/thalamus: 1.29 ± 0.59, Rap/thalamus: 7.02 ± 2.74 and Rap/GP 0.82 ± 0.39) (A), average seizure scale (Veh/thalamus: 1.06 ± 0.43, Rap/thalamus: 2.56 ± 0.41 and Rap/GP 0.64 ± 0.27) (B), and average number of stage 4 and 5 seizures (Veh/thalamus: 0.83 ± 0.41, Rap/thalamus: 4.25 ± 1.76 and Rap/GP 0.44 ± 0.29) (C) (ANOVA with Tukey post hoc adjustment; mean ± SEM; * indicates p<0.05; n=8–9). (D–F) Systemic administration of the KCC2 blocker furosemide (40 mg/kg) via i.p. injection 15 min prior to pilocarpine i.p. injection. Rats treated with furosemide showed a significant increase in seizure duration (control: 0.73 ± 0.16 vs furosemide: 5.17 ± 1.17) (D), average seizure scale (control: 1.03 ± 0.16 vs furosemide: 2.48 ± 0.30) (E), and average number of stage 4 and 5 seizures (control: 0.90 ± 0.23 vs furosemide: 3.13 ± 0.40) (F). (G–I) Furosemide or vehicle was delivered bilaterally to the thalamus via microinfusion 15 min prior to i.p. administration of pilocarpine. Rats treated with furosemide locally showed a significant increase in average seizure duration (control: 0.41 ± 0.27 vs furosemide: 4.54 ± 1.84) (G), average seizure scale (control: 0.52 ± 0.30 vs furosemide: 2.25 ± 0.56) (H), and average number of stage 4 and 5 seizures (control: 0.18 ± 0.18 vs furosemide: 3.36 ± 1.36) (I). (mean ± SEM; * indicates p<0.05; t-test; n=6–11).