Figure 7.
Selectively impaired working memory in NGR−/− mice. Mice were tested on a battery of tests to assess affective and cognitive responses. A, B, The light/dark exploration test was performed by placing the mouse in a cage (44 × 21 × 21 cm) that has one dark chamber (Dark) and one light chamber (Light). The animal was initially placed in the lighted side, and transitions between sides (trans) and the time spent in each chamber were recorded for 10 min using computer-monitored photocell beams. Mice were from a mixed 129 × C57BL/6 strain background. No significant difference of anxiety-like behavior was observed between WT and NGR−/− animals (n = 21, 10 WT, 11 −/−). C, The importance of NgR1 signaling to the spatial working memory functions of the prefrontal cortex in mice. NGR-deficient mice (−/−; n = 8) performed significantly worse on the spatial delayed alternation task than WT mice (+/+; n = 5). All mice were of a pure C57BL/6J genetic background (>10 backcrosses for the NGR mutation). Data represent mean ± SEM percentage correct over the 30 daily test sessions; *p = 0.017. D, NGR heterozygote and null littermate mice from a mixed strain background were subjected to a 2 d six-arm radial-arm water-maze paradigm as described previously (Morgan et al., 2000). To minimize odor cues, the goal arm was randomly assigned for each mouse. The start arm was varied for each trial, with the goal arm remaining constant. The mice were tested in the same manner on day 2. The number of incorrect arm entries (errors) was measured for 1 min. Mice made an arm choice within 20 s in every experiment. Each mouse's errors for five consecutive trials were averaged. E, Passive avoidance testing was performed in a mouse passive avoidance chamber (Ugo Basile). Mice used were from mixed 129 × C57BL/6 background. Testing occurred on 3 consecutive days; for all trials, the mouse was initially placed in the light chamber. On day 1, the mouse was allowed to move freely between the two compartments for 5 min. On day 2 (preshock), the entry latency into the dark chamber was measured; after entry, the door between the light and dark compartments closed, and a 2 s electric shock (0.2 mA) was administered through the grid floor. On day 3 (postshock), entry latency into the dark chamber was recorded. No differences in passive avoidance learning were observed in the WT and NGR−/− mice (n = 34, 17 WT, 17 −/−). F, Tyrosine hydroxylase-immunoreactive fibers in the prefrontal cerebral cortex and the caudate nucleus were visualized in sections from WT and NGR−/− adult mice. Scale bar, 100 μm. All data are mean ± SEM.
