Figure 2— Cntnap2 knockout (KO) rats exhibit seizures

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Figure 2— Cntnap2 knockout (KO) rats exhibit seizures Figure 2— Cntnap2 knockout (KO) rats exhibit seizures. (A) Representative example of seizures with electroencephalogram (EEG), electromyogram (EMG), and spectrogram corresponding to the EEG. The spectrogram was calculated using a 1-s Hanning window with 95% overlap and was normalized to the average spectral power for wakefulness (artifact/seizure-free periods) from a 24-hr EEG recording. Boxes denote recording periods plotted at an expanded time base below, demonstrating the variability of the waveforms during the seizure and post-ictal periods. (B) Average number of events during four 24-hr baseline (BL) recordings at either three or four months of age in KO rats (3 mo: n = 7; 4 mo: n = 4), and a 4-hr sleep deprivation (SDep) experiment followed by a 20-hr post-SDep recovery period at 3 months. BL recordings were conducted under undisturbed conditions. Individual colored symbols represent total events for each animal. “^” refers to 2 KO rats that died and 1 that lost its EEG signal before the recordings at 4 months of age. Values are means ± standard error of the mean (SEM). From: Cntnap2 Knockout Rats and Mice Exhibit Epileptiform Activity and Abnormal Sleep–Wake Physiology Sleep. 2016;40(1). doi:10.1093/sleep/zsw026 Sleep | © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Figure 3— Cntnap2 knockout (KO) mice exhibit seizure-like events Figure 3— Cntnap2 knockout (KO) mice exhibit seizure-like events. Examples of spike-like activity during rapid eye movement (REM) sleep (A) with electroencephalogram (EEG), electromyogram (EMG), and spectrogram corresponding to the EEG. The spectrogram was calculated using a 1-s Hanning window with 95% overlap and was normalized to the average spectral power for wakefulness (artifact/seizure-free periods) from a 24-hr EEG recording. (B) Average number of events observed during 24-hr recordings of wild-type (WT) and KO mice conducted at 4 and 8 months of age. Small circles represent individual animals to show the variability in seizure number. (C) Mean number of events plotted across the 24-hr period. (D) Distribution of events occurring in each vigilance state. Two states separated by a dash represent transitions between states. Values plotted as means ± standard error of the mean (SEM; n = 9–11/genotype). *p < .05, **p < .01. W, wake. From: Cntnap2 Knockout Rats and Mice Exhibit Epileptiform Activity and Abnormal Sleep–Wake Physiology Sleep. 2016;40(1). doi:10.1093/sleep/zsw026 Sleep | © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Figure 1— Cntnap2 knockout (KO) rats and mice have abnormal behavior Figure 1— Cntnap2 knockout (KO) rats and mice have abnormal behavior. Total distance traveled in theopen-field activity (OFA) assay (20 min) for rats (A) and mice (B). Total duration of social interactions in rats (C) and mice (D). Species-specific repetitive behaviors are reported as the percentage of object chewed in the chew test for rats (E) and grooming time during a self-grooming test in mice (F). Values plotted as means ± standard error of the mean (SEM; rats: n = 7–10/genotype; mice: n = 12/genotype). *p < .05, **p < .01. WT, wild-type. From: Cntnap2 Knockout Rats and Mice Exhibit Epileptiform Activity and Abnormal Sleep–Wake Physiology Sleep. 2016;40(1). doi:10.1093/sleep/zsw026 Sleep | © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Figure 4— Cntnap2 knockout (KO) rats are hyperactive while Cntnap2 KO mice are hypoactive. Hourly locomotor activity (LMA) counts over 24 hr for wild-type (WT) and KO rats (A) and mice (B). Corresponding 24-hr body temperature (T<sub>b</sub>) rhythms for rats (C) and mice (D). (E) Activity-independent 24-hr T<sub>b</sub> profile for rats, expressed as deviation from the mean. (F) Activity-independent rat T<sub>b</sub> plotted by light/dark phase, expressed as deviation from the mean. Values plotted as means ± standard error of the mean (SEM; rats: n = 10 WT, 7 KO; mice: n = 11 WT, 10 KO). *p < .05, **p < .01. Shaded areas in A-E indicate the 12-hr dark phase. ZT, zeitgeber time. From: Cntnap2 Knockout Rats and Mice Exhibit Epileptiform Activity and Abnormal Sleep–Wake Physiology Sleep. 2016;40(1). doi:10.1093/sleep/zsw026 Sleep | © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Figure 5— Cntnap2 knockout (KO) rats have fewer transitions between vigilance states. (A) Hourly percent time spent in wake (W). (B) Total number of W bouts and (C) mean W bout duration in the light and dark phases. (D) Hourly percent time spent in NREM sleep. (E) Total number of non-rapid eye movement (NREM) sleep bouts and (F) the mean NREM bout duration in the light and dark phases. (G) Hourly percent time spent in rapid eye movement (REM) sleep and total time in REM. (H) Total number of REM sleep bouts and (I) the mean REM bout duration in the light and dark phases. Values plotted as means ± standard error of the mean (SEM; n = 10 wild-type [WT], 7 KO). <sup>#</sup>p < .1, *p < .05, **p < .01. ZT, zeitgeber time. From: Cntnap2 Knockout Rats and Mice Exhibit Epileptiform Activity and Abnormal Sleep–Wake Physiology Sleep. 2016;40(1). doi:10.1093/sleep/zsw026 Sleep | © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Figure 8— Cntnap2 knockout (KO) rats and mice have normal homeostatic regulation of sleep. (A) Locomotor activity (LMA) counts and (B) body temperature (T<sub>b</sub>) in Cntnap2 rats during a 4-hr sleep deprivation (SDep) followed by an 8-hr recovery period. (C) LMA and (D) T<sub>b</sub> in Cntnap2 mice during a 6-hr SDep and 6-hr recovery period. The vertical dashed line represents the end of the SDep and the beginning of the recovery period. Electroencephalogram (EEG) delta power (0.5–5 Hz) during the recovery period for wild-type (WT) and KO rats (E) and mice (F). EEG delta power for each animal during the recovery period was normalized to that animal’s delta power during its baseline recording. Values plotted as means ± standard error of the mean (SEM; rats: n = 10 WT, 7 KO; mice: n = 7–11/genotype). *p < .05, ** p < 0.01. ZT, zeitgeber time. From: Cntnap2 Knockout Rats and Mice Exhibit Epileptiform Activity and Abnormal Sleep–Wake Physiology Sleep. 2016;40(1). doi:10.1093/sleep/zsw026 Sleep | © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Figure 6— Cntnap2 knockout (KO) mice have blunted diurnal rhythms of wake and non-rapid eye movement (NREM) sleep and fragmented bouts of wakefulness. (A) Hourly distribution of wake (W). (B) Total number of bouts spent in W and (C) the mean W bout duration in the light and dark phases. (D) Hourly distribution of NREM sleep. (E) Total number of bouts spent in NREM sleep and (F) the mean NREM bout duration in the light and dark phases. (G) Hourly distribution of rapid eye movement (REM) sleep. (H) Total number of bouts spent in REM sleep and (I) the mean REM bout duration in the light and dark phases. Values plotted as means ± standard error of the mean (SEM; n = 11 wild-type [WT], 10 KO). <sup>#</sup>p < .1, *p < .05, **p < .01. ZT, zeitgeber time. From: Cntnap2 Knockout Rats and Mice Exhibit Epileptiform Activity and Abnormal Sleep–Wake Physiology Sleep. 2016;40(1). doi:10.1093/sleep/zsw026 Sleep | © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Figure 7— Cntnap2 knockout (KO) rats and mice have decreased alpha power during wakefulness. (A) Electroencephalogram (EEG) spectra during wake (W) in wild-type (WT) and KO rats and (B) mice. (C) EEG spectra during non-rapid eye movement (NREM) sleep in WT and KO rats and (D) mice. (E) EEG spectra during rapid eye movement (REM) sleep in WT and KO rats and (F) mice. Spectral and bar plots represent the relative EEG spectral power for the 24-hr period, normalized for each state to the 24 hr mean power for that state in the WT group of that species. Values plotted as means ± standard error of the mean (SEM; rats: n = 10 WT, 7 KO; mice: n = 7 WT, 9 KO). *p ≤ .01. The bar under the spectral plots represents individual points where p ≤ .05. From: Cntnap2 Knockout Rats and Mice Exhibit Epileptiform Activity and Abnormal Sleep–Wake Physiology Sleep. 2016;40(1). doi:10.1093/sleep/zsw026 Sleep | © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.