Figure 4.

Double KO mice are impaired in a gap-in-noise detection task. (A) Locomotor activity test in a novel environment shows a similar number of beam breaks per 10 min for WT and double KO mice over the course of 90 min (P > 0.05). (B, C) Double KO mice display a suggestive increase in anxiety-like behavior by spending more time in the dark area in the light–dark box (B, P = 0.06) but that was accompanied also by a decrease in overall locomotor activity in the chamber (C, P = 0.01). (D–F) Spatial memory in dKO was unaffected as indicated by similar percentage of arm alternations in the T-maze when compared to WT controls (D), and similarly for exploration in the Y-maze indicated by time spent (E) and number of entries (F) in a novel arm. (G) No differences are detected in the percentage of startle inhibition displayed by WT and dKO mice when presented with stimuli as shown in I. (H) Double KO mice show lower inhibition of startle reflex in a silent gap detection task (see J), with significant differences at certain gap durations (2 ms, P = 0.03, d = 0.76; 5 ms, P = 0.04, d = 0.57; 30 ms, P = 0.01, d = 0.84; 40 ms, P = 0.04; d = 0.77). All data shown as means ± SEM (n = 18 per genotype). (I) Diagram of stimuli used in prepulse inhibition protocol; a startle-eliciting stimulus of 120 dB SPL and 40 ms duration was presented alone (uncued trial) or 100 ms after offset of a 20 ms prepulse of varying sound intensity levels above background noise (65 dB SPL) (cued trials) (full protocol diagram shown in Fig. S10G). (J) Diagram of stimuli used in silent gap detection protocol; a startle-eliciting stimulus of 105 dB SPL and 50 ms duration was presented alone (uncued trial) or 100 ms after offset of a silent gap of varying duration in the background noise (75 dB SPL) (cued trials) (full protocol diagram shown in Fig. S10H).