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. 2014 Aug 13;76(3):443–456. doi: 10.1002/ana.24230

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© 2014 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Tau ablation reduces epileptic activity in Scn1a^RX/+ mice. (A–C) Subdural electroencephalographic (EEG) recordings were obtained in freely behaving mice of the indicated genotypes at 2 to 3 months of age. For the traces in (A) and (B), the low and high frequency filters were set at 5Hz and 40Hz, respectively. (A) Representative EEG trace depicting a seizure in an Scn1a^RX/+ mouse. This seizure (highlighted in gray) lasted 30 seconds and had a severity score of 4 (see Materials and Methods). Scale bars = 3 sec (horizontal), 0.25V (vertical). (B) Representative traces of interictal EEG activity. Note the spikes (arrowheads) in Scn1a^RX/+/Tau^+/+ mice. Scale bars = 0.3 sec (horizontal), 0.5V (vertical). (C) Quantitation of epileptic spikes during 1 hour of a 24-hour recording session (n = 6–24 mice per genotype). Linear regression: p = 0.0030, F_1,58 = 11.08 for an interaction between Scn1a and Tau genotypes. Gene–dose effect of Tau deletion in Scn1a^RX/+ mice: p = 0.0000054 (Wald test). Exploratory post hoc 1-tailed t tests without multiple comparison correction indicated that Scn1a^RX/+/Tau^+/− mice differed from both Scn1a^RX/+/Tau^+/+ (p = 0.0085) and Scn1a^+/+/Tau^+/+ mice (p = 0.0087). ***p < 0.00001 versus Scn1a^+/+/Tau^+/+ mice or as indicated by bracket (Tukey–Kramer test). (D–F) Epileptiform activity in acute hippocampal slices from mice of the indicated genotypes was elicited by superfusion with picrotoxin (50μM) and 4-aminopyridine (200μM) for 30 minutes. (D) Representative field recordings of epileptic activity. Higher resolution traces are shown on the right, depicting individual spikes and a burst of multiple spikes recorded in the Scn1a^RX/+ slice. Scale bars in main traces: 20 seconds (horizontal), 0.5mV (vertical); insets: 250 milliseconds (horizontal), 1.0mV (vertical). (E) Quantification of spike frequency. (F) Quantification of burst frequency (n = 3–6 mice per genotype and 17–27 slices per mouse). *p < 0.05, **p < 0.01, ***p < 0.001 versus Scn1a^+/+/Tau^+/+ slices or as indicated by bracket (linear mixed effects model). Values represent mean ± standard error of the mean. [Color figure can be viewed in the online issue, which is available at http://www.annalsofneurology.org.]