Figure 1: Spatial learning and memory and CA1 LTP deficits in Pyk2 mutant mice.

(a) In the spontaneous alternation test, Pyk2^+/+, Pyk2^+/− and Pyk2^−/− 3-month-old mice were placed for 10 min in a Y-maze with one arm closed (upper left panel). Two hours later, they were put in the same maze with the new arm (NA) open and the percentage of time exploring the NA and the previously explored (old arm, OA) was compared (upper right panel). Two-way ANOVA interaction F_(2,48)=11.6, P<0.0001, OA versus NA Holm-Sidak’s test, Pyk2^+/+, t=4.6, P<0.0001, Pyk2^+/−, t=1.58, Pyk2^−/−, t=0.81. (b) In the NOL test, the percentage of time exploring the displaced object (new location, NL, 24 h after first exposure) and the unmoved object (old location, OL) was compared (upper panels). Two-way ANOVA interaction F_(2,50)=3.41, P=0.041, OL versus NL Holm-Sidak’s test, Pyk2^+/+, t=3.1, P<0.01, Pyk2^+/−, t=0.23, Pyk2^−/−, t=0.14. In a,b, 7–12 mice were used per genotype; the red dotted line indicates the chance level. (c,d) Schaffer collaterals were stimulated in hippocampal slices (one–three slices per animal) from 3-4-week-old Pyk2^+/+ (n=5), Pyk2^+/− (n=6) and Pyk2^−/− (n=4) mice, and fEPSP were recorded in CA1, before and after HFS (5 × 1 s at 100 Hz). (c) Time course of fEPSP slope. Insets show typical traces before (grey) and 40 min after (black) HFS in Pyk2^+/+ and Pyk2^−/− slices. (d) Ten-min average of fEPSP slope 40 min after HFS, normalized to the mean of 10- min baseline (corresponding time points are indicated in c by grey and black horizontal lines). Kruskal–Wallis=9.37, P=0.0024, post hoc analysis with Dunn’s multiple comparisons test. (e) Paired-pulse ratio (50-ms interval, see Supplementary Fig. 1e) at the same synapses. n=3–5 mice per group, two–four slices per mouse. Kruskal–Wallis=15.62, P=0.0004. In a–e, values are means+s.e.m., *P<0.05, **P<0.01, ***P<0.001.