Contextual and serial discriminations: a new learning paradigm to assess simultaneously the effects of acute stress on retrieval of flexible or stable information in mice

Abstract

The present study was aimed at simultaneously determining on the same subject, the effects of stress on retrieval of flexible (contextual or temporal) or stable (spatial) information. Three behavioral paradigms carried out in a four-hole board were designed as follows: (1) Simple Discrimination (SD), in which mice learned a single discrimination; (2) Contextual and Serial Discriminations (CSD), in which mice learned two successive discriminations on two different internal contexts; (3) Spatial Serial Discriminations (SSD), in which mice learned two successive discriminations on an identical internal context. The stressor (three inescapable electric footshocks) was delivered 5 min before retention, occurring 5 min or 24 h after acquisition. Results showed that this stressor increased plasmatic corticosterone levels and fear reactivity in an elevated-plus-maze, as compared with nonstressed mice. The stressor reversed the normal pattern of retrieval observed in nonstressed controls in the CSD task, this effect being context dependent, as it was not observed in the SSD task. Overall, our study shows that stress affected the retrieval of flexible and old information, but spared the retrieval of stable or recent ones. Therefore, these behavioral paradigms allow us to study simultaneously, on the same animal, the effects of stress on distinct forms of memory retrieval.

Figure 1

Effect of acute stress (three inescapable electric footshocks) on HPA (hypothalamo-pituitary-adrenal) axis response amplitude measured by radioimmunoassay (RIA) of plasma corticosterone level for Stressed mice (S), nonstressed mice (NS), and quiet controls. Acute stress induced a significant increase of plasma corticosterone level as compared with nonstressed mice and quiet controls (^**) P < 0.01.

Figure 2

Time course of corticosterone release after acute stress. Corticosterone level of stressed mice reached a maximal value 10 min after footshock stimulation, and decreased progressively to get back to basal level between 60 and 120 min after stress (^**) P < 0.01; (^***) P < 0.001.

Figure 3

Study of emotional reactivity in the elevated-plus-maze for stressed mice (S) and nonstressed mice (NS). Acute stress had an anxiogenic like effect, as it significantly reduced the number of visits in open arms and in the four arms as compared with nonstressed animals (^*) P < 0.05.

Figure 4

Results of Simple Discrimination task (SD) for the 5-min (left) and 24-h (right) retention intervals. Results are expressed in percent exploration in the correct hole (previously baited hole) for the stressed mice (S) and nonstressed mice (NS). Chance level was 25% (one baited hole over four). Performances were significantly above chance level for the two retention intervals (oooo) P < 0.0001; (oo) P < 0.01; (o) P < 0.05 as compared with chance level. Performances were better for the 5-min than for the 24-h retention interval (^***) P < 0.001. Acute stress had no effect on performances whatever the retention interval.

Figure 5

Results of Contextual Serial Discriminations task (CSD) for the 5-min (left) and 24-h (right) retention intervals. Results are expressed in percent exploration in the correct hole (previously baited hole in the same internal context) and in the interfering hole (previously baited hole in the other internal context) for the stressed mice (S) and nonstressed mice (NS). Acute stress modulated performances for the 24-h retention interval (but not for the 5-min retention interval) by producing an inversion of the serial order spontaneously expressed by nonstressed mice. This modulation depended on variations of proactive and retroactive interference (ooo) P < 0.001; (oo) P < 0.01; (o) P < 0.05 as compared with chance level, and (^**) P < 0.01; (^*) P < 0.05).

Figure 6

Results of Spatial and Serial Discriminations task (SSD) for the 24-h retention interval. Results are expressed in percent exploration in the first hole (1: first previously baited hole) and in the second hole (2: second previously baited hole) for the stressed mice (S) and nonstressed mice (NS). Acute stress did not produce an inversion of serial order when the two successive discriminations took place in the same internal context. (oo) P < 0.03; (o) P < 0.04 as compared with chance level, and (^*) P < 0.05).

Figure 7

Behavioral procedures of the three experimental tasks; SD (top); CSD (middle), and SSD (bottom). Rooms A, B, and C were different.