Figure 1

JQ1 improves cognitive performance in the fear-conditioning and water maze test without affecting basal motor and exploratory behavior. (a) Left panel: path per minute in the open field was not changed in JQ1-injected animals. n=10 (vehicle); 9 (JQ1). Right panel: total path in the open field was not changed in JQ1-injected animals. n=10 (vehicle); 9 (JQ1). (b) The latency to fall during the training phase of the rotarod test did not show significant differences between vehicle- and JQ1-injected animals. n=14 (vehicle); 14 (JQ1). (c) Left panel: latency to fall from the rod in the rotarod test was not different in JQ1-treated animals. n=14 (vehicle); 14 (JQ1). Right panel: the speed at which animals fell in the rotarod test was not different for JQ1-treated animals. n=14 (vehicle); 14 (JQ1). (d) A single JQ1 i.p. injection after training the contextual fear-conditioning paradigm led to increased freezing levels in JQ1-treated animals. *P<0.05, two-tailed Student’s t-test. n=8 (vehicle); 10 (JQ1). (e) Freezing levels are elevated in JQ1-treated animals when they were tested 4 weeks after training. ***P<0.001, two-tailed Student’s t-test. n=15 (vehicle); 15 (JQ1). (f) Left panel: JQ1 injections into the hippocampus (i.h.) before the training led to a significant increase in freezing levels in wild-type animals. *P<0.05, two-tailed Student’s t-test. n=9 (vehicle); 10 (JQ1); right panel: a single intrahippocampal JQ1 injection immediately after training in the fear-conditioning paradigm caused a borderline significant increase in freezing levels at an alpha level of 0.1. P-value from a two-tailed Student’s t-test. n=9 (vehicle); 8 (JQ1). (g) Escape latency of wild-type animals that received daily JQ1 injections after the training session in the MWM performed is similar to that of vehicle-injected animals. n=18 (vehicle); 16 (JQ1). (h) JQ1-treated animals spent significantly more time in the target area where the escape platform was during training, in the probe test. **P<0.01, two-tailed Student’s t-test. n=18 (vehicle); 16 (JQ1). Left panel shows heatmap occupancy plots representing the probe test for vehicle- and JQ1-injected animals. Brighter colors indicate higher occupancy. (i) Dose-dependent increase in LTP recorded from wild-type slices treated with vehicle or with increasing doses of JQ1 per bath application. *P<0.05, repeated measures ANOVA, F (1,12)=5.127; n=5 (vehicle); 10 (JQ1). Error bars indicate s.e.m. EPSP, excitatory postsynaptic potential; MWM, Morris Water Maze.