Fig. 1

Shank3 KO mice are hyperexcitable and show an altered gain control. A left: Representative electrophysiological traces of up and down states in Wt (black, top) and Shank3 KO (red, bottom) anesthetized mice with the respective spectrograms. USs are indicated with a bar. Scale bar 0.2 mV, 0.5 s. Color map for spectrograms: -80, -20 dB. Middle: Analysis of slow-wave activity in the same experimental groups shows increased duration of USs in Shank3 KO mice (Wt, N = 14 mice, n = 40 traces; Shank3 KO, N = 11 mice, n = 31 traces; Mann–Whitney Test, *p < 0.05), where up and down states were identified automatically by selecting power in gamma band. Right: US 25-80 Hz RMS Power is significantly different (Mann–Whitney Test, *p < 0.05). B top: Mean power spectra of LFP in anesthetized mice. Lines indicate the mean power spectra and the shaded areas indicate the SEM (N = 14 Wt, N = 11 Shank3 KO). Bottom, difference between Shank3 KO and Wt average power spectra. Shank3 KO mice are not openly epileptic; however, spectral analysis of the resting state under urethane anesthesia shows increased spectral power at all frequencies between a few Hz to about 100 Hz; in particular, there is a diffused increase in the beta (10–25 Hz) and gamma frequency band (25-80 Hz) (Mann–Whitney rank test over frequency window from 10-20 Hz to 90-100 Hz; ***p < 0.001). The two spectral distributions are not different below 2 Hz. C Experimental paradigm and exemplificative VEPs to alternating checkerboards. Dotted lines indicate the checkerboard reversal. D Contrast sensitivity curve is significantly different in Shank3 KO (N = 17) versus Wt mice (N = 17) (two-way ANOVA, Holm-Sidak test; ***p < 0.001), with Shank3 KO mice showing fast saturation of the response curve at lower contrast value. The continuous lines here and in panel F are Michaelis–Menten fits to the data. E Exemplificative waveforms of responses to alternating checkerboards (red, Shank3 KO; magenta, Shank3 KO after midazolam superfusion over the cortex). Scale bars: 0.1 mV, 0.5 s. F Contrast sensitivity curve is significantly different in Shank3 KO treated with vehicle (N = 6) versus Shank3 KO + Midazolam mice (N = 6) and it is evident a rescue to control situation after superfusion with Midazolam (Wt, N = 17; 5 mg/ml; two-way ANOVA; **p = 0.003). G Analysis of contrast sensitivity curves, as quantified by the Michaelis–Menten fittings (Wilcoxon Signed Ranks Test; * p = 0.035)