Fig. 1
Spatial memory, CREB-dependent gene expression, L-LTP are impaired in γCaMKII-deficient mice. a Spatial memory acquisition and retrieval were tested with the Morris Water Maze (MWM). Bottom left, mean escape latencies to reach a hidden platform were plotted against training day (4 trials per day) for WT mice (black, n = 21 for 1st 3 days, 12 for 4th day) and γCaMKII KO mice (red, n = 19 for 1st 3 days, 10 for 4th day). Top left, representative path used by mice to reach hidden platform (dotted circle) during the last trial of Day 4. Top right, activity histogram representing average proportion of total time spent by mice during probe trial; γCaMKII KO mice (n = 10), WT (n = 12); scale at far right, amount of time spent at different locations. Bottom middle, latency to reach platform zone during probe trial. Bottom right, number of zone entries during probe trial. b Western blot analysis of BDNF, c-Fos, and Arc expression in the hippocampus of WT (black, n = 9) and KO (red, n = 7) mice. Animals sacrificed 1 h after end of MWM training on 3rd day. c Inset, schematic depiction of inhibitory avoidance test. Left graph, cumulative distribution of latencies to enter the dark compartment before conditioning (dashed lines) and 24 h post conditioning (solid lines). Conditioning done by administration of a mild shock in the dark compartment. Right bar graph, percentage of c-Fos+ neurons in CA1 assessed 1 h after test trial. d Left, late-phase LTP (L-LTP) induced by three trains of tetanic stimulation (100 Hz, 1 s), spaced by 5 min intervals24,37, with timing denoted by the gap in the field EPSP trace (n = 6 mice for each group). Superimposed representative EPSPs show the basal EPSP (bold color) and the EPSP at 165 min (muted color) after L-LTP induction. Calibration bars, 1 mV and 10 ms. Top right, Fluo-4 Ca2+ responses (ΔF/F) to 5 s of 100 Hz field stimulation in acute hippocampal slices from wild-type and γCaMKII KO mice. Bottom right, paired-pulse ratio (slope of second EPSP/slope of first EPSP) plotted with interpulse intervals of 50, 100, and 200 ms (n ≥ 9 slices). e Radial arm maze behavior. Reference and working memory on day 2, reflecting various aspects of spatial memory 24 h after first exposure to maze, were assayed respectively by recording the number of entries into arms that were never baited (reference memory) or re-entries into arms that were initially baited (working memory) (n ≥ 9 for both genotypes). Statistical analysis was performed with one-way ANOVA followed by Holm–Sidak post hoc test unless otherwise noted. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001. Error bars represent SEM
