Article Figures & Data
Figures
- Figure 1.
Genetic blockade of CA3 synaptic transmission attenuates acute KA-induced seizures. A, The mean behavioral seizure score following kainic acid injection was significantly reduced in CA3-TeTX mice. Analysis revealed that (B) the fraction of CA3-TeTX mice reaching stage 3 seizures (forelimb clonus and rearing) was reduced compared with control mice. The mutant mice also had (C) a significantly lower maximal seizure score and (D) a lower cumulative seizure score than control mice. ****p<0.0001, ***p<0.001, **p<0.01. Control, n=9; CA3-TeTX n=9.
- Figure 2.
Loss of CA3 output causes a decrease in c-fos expression in the CA3 and CA1 subfields following KA-induced seizure. A, Examples of c-fos protein expression in the dorsal hippocampus of control (top) and CA3-TeTX (bottom) mice 2.5 h after injection with kainic acid (left) or saline (right). Quantification of the fluorescent c-fos expression signal finds significantly higher signal in the (B) CA1 and (C) CA3 regions of the control mice injected with KA compared with the CA3-TeTX/KA and both saline groups. However, in the (D) DG, robust c-fos expression was evident in both genotypes following KA injection. ***p<0.001. Control + KA, n=7; control + saline, n=6; CA3-TeTX + KA, n=8; CA3-TeTX + saline, n=4.
- Figure 3.
Loss of CA3 output prevents increases in CA1 oscillations induced by KA. A, Example LFP recordings in CA1 stratum radiatum from a control (blue; top) and CA3-TeTX (red; bottom) mouse 60 min after kainic acid injection. For each genotype the top panel shows the raw LFP, the second panel the theta band filtered LFP, the third the slow gamma filtered LFP, and the bottom the fast gamma filtered LFP. Note the scale in the control traces is 10× that of the CA3-TeTX mice. KA injection lead to a significant increase in power in the (B) theta band and the (C) slow gamma band 35 min postinjection, and in the (D) fast gamma band 25 min following KA. ****p<0.0001, ***p<0.001, **p<0.01, *p<0.05. Control, n=22 (control ON DOX, n=12; control OFF DOX, n=4; CA3-TeTX ON DOX, n=6); CA3-TeTX, n=16.
Tables
Data structure Type of test Observed power (α=0.05) a Normally distributed Two-way repeated-measure ANOVA <0.0001 Bonferroni multiple comparisons (CA3-TeTX × control) 0 >0.05 10 >0.05 20 >0.05 30 <0.01 40 <0.0001 50 <0.001 60 <0.0001 70 <0.0001 80 <0.0001 90 <0.0001 100 <0.0001 110 <0.0001 120 <0.0001 b Normally distributed Unpaired t test <0.0001 c Normally distributed Welch t test 0.0002 d Normally distributed Two-way ANOVA (genotype × drug) 0.003 Bonferroni multiple comparisons (KA vs saline) KA <0.0001 Saline >0.05 e Normally distributed Two-way ANOVA (genotype × drug) 0.0011 Bonferroni multiple comparisons (KA vs saline) KA <0.001 Saline >0.05 f Normally distributed Two-way ANOVA (genotype × drug) 0.0757 Two-way repeated-measure ANOVA (genotype) 0.6035 Two-way repeated-measure ANOVA (drug) <0.0001 Bonferroni multiple comparisons (KA vs saline) KA >0.05 Saline >0.05 g Normally distributed Two-way repeated-measure ANOVA (time × control group) Theta (time × group) 0.9996 Theta (time) <0.0001 Theta (group) 0.8227 Low gamma (time × group) 0.7955 Low gamma (time) <0.0001 Low gamma (group) 0.405 High gamma (time × group) 0.9379 High gamma (time) <0.0001 High gamma (group) 0.3334 h Normally distributed Two-way repeated-measure ANOVA (time × group) theta band <0.0001 Bonferroni multiple comparisons (CA3-TeTX × control ON DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p>0.05 45 p<0.05 50 p<0.01 55 p<0.001 60 p<0.001 65 p<0.001 70 p<0.001 75 p<0.0001 80 p<0.0001 85 p<0.0001 90 p<0.0001 95 p<0.0001 100 p<0.0001 105 p<0.0001 Bonferroni multiple comparisons (CA3-TeTX × control OFF DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p<0.05 40 p<0.05 45 p<0.01 50 p<0.05 55 p<0.05 60 p<0.01 65 p<0.05 70 p<0.05 75 p>0.05 80 p>0.05 85 p>0.05 90 p<0.01 95 p<0.05 100 p<0.01 105 p<0.01 Bonferroni multiple comparisons (CA3-TeTX × CA3-TeTX ON DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p>0.05 45 p>0.05 50 p>0.05 55 p>0.05 60 p>0.05 65 p>0.05 70 p>0.05 75 p<0.05 80 p<0.01 85 p<0.01 90 p<0.01 95 p<0.001 100 p<0.001 105 p<0.0001 Bonferroni multiple comparisons (control ON DOX × control OFF DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p>0.05 45 p>0.05 50 p>0.05 55 p>0.05 60 p>0.05 65 p>0.05 70 p>0.05 75 p>0.05 80 p>0.05 85 p>0.05 90 p>0.05 95 p>0.05 100 p>0.05 105 p>0.05 Bonferroni multiple comparisons (control ON DOX × CA3-TeTX ON DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p>0.05 45 p>0.05 50 p>0.05 55 p>0.05 60 p>0.05 65 p>0.05 70 p>0.05 75 p>0.05 80 p>0.05 85 p>0.05 90 p>0.05 95 p>0.05 100 p>0.05 105 p>0.05 Bonferroni multiple comparisons (control OFF DOX × CA3-TeTX ON DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p>0.05 45 p>0.05 50 p>0.05 55 p>0.05 60 p>0.05 65 p>0.05 70 p>0.05 75 p>0.05 80 p>0.05 85 p>0.05 90 p>0.05 95 p>0.05 100 p>0.05 105 p>0.05 Normally distributed Two-way repeated-measure ANOVA (time × group) low gamma band <0.0001 Bonferroni multiple comparisons (CA3-TeTX × control ON DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p<0.05 45 p<0.01 50 p<0.0001 55 p<0.0001 60 p<0.0001 65 p<0.0001 70 p<0.0001 75 p<0.0001 80 p<0.0001 85 p<0.0001 90 p<0.0001 95 p<0.0001 100 p<0.0001 105 p<0.001 Bonferroni multiple comparisons (CA3-TeTX × control OFF DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p>0.05 45 p>0.05 50 p>0.05 55 p>0.05 60 p>0.05 65 p>0.05 70 p>0.05 75 p>0.05 80 p>0.05 85 p>0.05 90 p>0.05 95 p>0.05 100 p>0.05 105 p>0.05 Bonferroni multiple comparisons (CA3-TeTX × CA3-TeTX ON DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p>0.05 45 p>0.05 50 p<0.05 55 p>0.05 60 p>0.05 65 p>0.05 70 p>0.05 75 p>0.05 80 p>0.05 85 p>0.05 90 p>0.05 95 p>0.05 100 p>0.05 105 p>0.05 Bonferroni multiple comparisons (control ON DOX × control OFF DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p>0.05 45 p>0.05 50 p>0.05 55 p>0.05 60 p>0.05 65 p>0.05 70 p>0.05 75 p>0.05 80 p>0.05 85 p>0.05 90 p>0.05 95 p>0.05 100 p>0.05 105 p>0.05 Bonferroni multiple comparisons (control ON DOX × CA3-TeTX ON DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p>0.05 45 p>0.05 50 p>0.05 55 p>0.05 60 p>0.05 65 p>0.05 70 p>0.05 75 p>0.05 80 p>0.05 85 p>0.05 90 p>0.05 95 p>0.05 100 p>0.05 105 p>0.05 Bonferroni multiple comparisons (control OFF DOX × CA3-TeTX ON DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p>0.05 45 p>0.05 50 p>0.05 55 p>0.05 60 p>0.05 65 p>0.05 70 p>0.05 75 p>0.05 80 p>0.05 85 p>0.05 90 p>0.05 95 p>0.05 100 p>0.05 105 p>0.05 Normally distributed Two-way repeated-measure ANOVA (time × group) high gamma band <0.0001 Bonferroni multiple comparisons (CA3-TeTX × control ON DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p<0.001 35 p<0.01 40 p<0.001 45 p<0.001 50 p<0.001 55 p<0.0001 60 p<0.0001 65 p<0.001 70 p<0.001 75 p<0.001 80 p<0.01 85 p<0.01 90 p<0.01 95 p<0.05 100 p<0.05 105 p<0.05 Bonferroni multiple comparisons (CA3-TeTX × control OFF DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p>0.05 45 p>0.05 50 p>0.05 55 p>0.05 60 p>0.05 65 p>0.05 70 p>0.05 75 p>0.05 80 p>0.05 85 p>0.05 90 p>0.05 95 p>0.05 100 p>0.05 105 p>0.05 Bonferroni multiple comparisons (CA3-TeTX × CA3-TeTX ON DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p<0.01 45 p<0.01 50 p<0.01 55 p>0.05 60 p>0.05 65 p>0.05 70 p>0.05 75 p>0.05 80 p>0.05 85 p>0.05 90 p>0.05 95 p>0.05 100 p>0.05 105 p>0.05 Bonferroni multiple comparisons (control ON DOX × control OFF DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p>0.05 45 p>0.05 50 p>0.05 55 p>0.05 60 p>0.05 65 p>0.05 70 p>0.05 75 p>0.05 80 p>0.05 85 p>0.05 90 p>0.05 95 p>0.05 100 p>0.05 105 p>0.05 Bonferroni multiple comparisons (control ON DOX × CA3-TeTX ON DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p>0.05 45 p>0.05 50 p>0.05 55 p>0.05 60 p>0.05 65 p>0.05 70 p>0.05 75 p>0.05 80 p>0.05 85 p>0.05 90 p>0.05 95 p>0.05 100 p>0.05 105 p>0.05 Bonferroni multiple comparisons (control OFF DOX × CA3-TeTX ON DOX) −20 p>0.05 −15 p>0.05 −10 p>0.05 −5 p>0.05 0 p>0.05 5 p>0.05 10 p>0.05 15 p>0.05 20 p>0.05 25 p>0.05 30 p>0.05 35 p>0.05 40 p>0.05 45 p>0.05 50 p>0.05 55 p>0.05 60 p>0.05 65 p>0.05 70 p>0.05 75 p>0.05 80 p>0.05 85 p>0.05 90 p>0.05 95 p>0.05 100 p>0.05 105 p>0.05 i Normally distributed Two-way repeated-measure ANOVA (time × group) <0.0001 Bonferroni multiple comparisons (CA3-TeTX × control) −20 >0.05 −15 >0.05 −10 >0.05 −5 >0.05 0 >0.05 5 >0.05 10 >0.05 15 >0.05 20 >0.05 25 >0.05 30 >0.05 35 <0.05 40 <0.01 45 <0.0001 50 <0.0001 55 <0.0001 60 <0.0001 65 <0.0001 70 <0.0001 75 <0.0001 80 <0.0001 85 <0.0001 90 <0.0001 95 <0.0001 100 <0.0001 105 <0.0001 j Normally distributed Two-way repeated-measure ANOVA (time × group) <0.0001 Bonferroni multiple comparisons (CA3-TeTX × control) −20 >0.05 −15 >0.05 −10 >0.05 −5 >0.05 0 >0.05 5 >0.05 10 >0.05 15 >0.05 20 <0.05 25 <0.01 30 <0.0001 35 <0.0001 40 <0.0001 45 <0.0001 50 <0.0001 55 <0.0001 60 <0.0001 65 <0.0001 70 <0.0001 75 <0.0001 80 <0.0001 85 <0.001 k Normally distributed Two-way repeated-measure ANOVA (time × group) <0.0001 Bonferroni multiple comparisons (CA3-TeTX × control) −20 >0.05 −15 >0.05 −10 >0.05 −5 >0.05 0 >0.05 5 >0.05 10 >0.05 15 >0.05 20 >0.05 25 <0.05 30 <0.01 35 <0.001 40 <0.0001 45 <0.0001 50 <0.0001 55 <0.0001 60 <0.001 65 <0.001 70 <0.01 75 <0.01 80 <0.01 85 <0.01 90 <0.01 95 <0.01 100 <0.01 105 <0.05
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