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. 2012;7(10):e48043.
doi: 10.1371/journal.pone.0048043. Epub 2012 Oct 22.

Environmental Enrichment Enhances Episodic-Like Memory in Association With a Modified Neuronal Activation Profile in Adult Mice

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Free PMC article

Environmental Enrichment Enhances Episodic-Like Memory in Association With a Modified Neuronal Activation Profile in Adult Mice

Marianne Leger et al. PLoS One. .
Free PMC article

Abstract

Although environmental enrichment is well known to improve learning and memory in rodents, the underlying neuronal networks' plasticity remains poorly described. Modifications of the brain activation pattern by enriched condition (EC), especially in the frontal cortex and the baso-lateral amygdala, have been reported during an aversive memory task in rodents. The aims of our study were to examine 1) whether EC modulates episodic-like memory in an object recognition task and 2) whether EC modulates the task-induced neuronal networks. To this end, adult male mice were housed either in standard condition (SC) or in EC for three weeks before behavioral experiments (n = 12/group). Memory performances were examined in an object recognition task performed in a Y-maze with a 2-hour or 24-hour delay between presentation and test (inter-session intervals, ISI). To characterize the mechanisms underlying the promnesiant effect of EC, the brain activation profile was assessed after either the presentation or the test sessions using immunohistochemical techniques with c-Fos as a neuronal activation marker. EC did not modulate memory performances after a 2 h-ISI, but extended object recognition memory to a 24 h-ISI. In contrast, SC mice did not discriminate the novel object at this ISI. Compared to SC mice, no activation related to the presentation session was found in selected brain regions of EC mice (in particular, no effect was found in the hippocampus and the perirhinal cortex and a reduced activation was found in the baso-lateral amygdala). On the other hand, an activation of the hippocampus and the infralimbic cortex was observed after the test session for EC, but not SC mice. These results suggest that the persistence of object recognition memory in EC could be related to a reorganization of neuronal networks occurring as early as the memory encoding.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Brain activation experimental design. A.
After 3 weeks in either standard condition (SC) or enriched condition (EC), memory performances of mice were tested in an object-recognition task performed in a Y-maze with an inter-session interval (ISI) of 24 h (“Test” groups, n = 12 for each housing condition). B. Ninety minutes after the presentation or after the test session, animals were euthanized and the brains were collected for c-Fos immunohistochemistry (“Presentation” groups and “Test” groups, n = 10 per housing condition). Additional mice were exposed to the same behavioral procedures but without any object (“Control of presentation” groups and “Control of test” groups, n = 8 and n = 10 per housing condition respectively).
Figure 2
Figure 2. Effect of increasing ISI on object recognition memory performances in mice housed in SC.
Data are expressed as the mean exploration time (± SEM) of novel object for the test session with increasing ISI: 2 h (n = 10), 4 h (n = 11), 6 h (n = 11) and 24 h (n = 12). Exploration time of the novel object was significantly higher than the chance level (10 seconds) with 2 h and 4 h-ISI, suggesting that SC mice discriminated the novel object at both delays (univariate t-test: § denotes P<0.05).
Figure 3
Figure 3. Effect of EC on object recognition memory tested with 2 h-ISI. A.
Data are the mean exploration time (± SEM) of the novel object during the test session in SC (n = 11) and EC (n = 9) groups. Exploration time of the novel object was significantly higher than the chance level (10 seconds) in the two groups (univariate t-test: § denotes P<0.05 for SC mice and EC mice), suggesting that all mice discriminated the novel object. Neither the percentage of entries, nor the percentage of time spent in the arm containing the novel object were different from the chance level (50%) in both groups. B. The time spent to reach the criterion (20 seconds of total exploration of the objects) did not differ between groups during the presentation session. By contrast, during the test session, the time spent to reach the criterion was significantly higher in EC mice than in SC ones (ANOVA with repeated measurements followed by a SNK multiple range test: ** denotes P<0.01, significantly different from SC group). The time spent to reach the criterion was significantly different between two sessions in EC group (ANOVA: # denotes P<0.05, significantly different from the presentation session). C. The total number of entries in the three arms did not differ between groups.
Figure 4
Figure 4. Effect of EC on object recognition memory tested with 24 h-ISI. A.
Data are the mean exploration time (± SEM) of the novel object during the test session in SC (n = 10) and EC (n = 10) groups. Only EC mice discriminated the novel object compared to the chance level (10 seconds) (univariate t-test: §§§ denotes P<0.001). Moreover, the time spent to explore the novel object was significantly higher in EC mice compared to SC ones (ANOVA: *** denotes P<0.001). The percentage of entries and the percentage of time spent in the arm containing the novel object were significantly different from the chance level (50%) in EC group only (univariate t-test: § denotes P<0.05). A significant difference of the percentage of time spent in the arm containing the novel object was observed between groups (ANOVA: * denotes P<0.05). B. The time spent to reach the criterion did not differ between groups during the presentation session but was significantly higher in EC mice during the test session (ANOVA with repeated measurements followed by a SNK multiple range test: ** denotes P<0.01, significantly different from SC group). EC mice spent significantly more time reaching the criterion during the test session (ANOVA: ## denotes P<0.01, significantly different from the presentation session). C. The total number of entries in the three arms did not differ between groups.
Figure 5
Figure 5. Effect of EC on neuronal activity in selected brain regions.
Results are expressed as mean percentage changes of relative number of c-Fos-positive cells compared to control animals (which performed the task without any objects: n = 8 “control of presentation” animals per housing condition for the presentation session and n = 10 “control of test” animals per housing condition for the test session). A. A significant activation of the hippocampus and the perirhinal cortex was observed in SC mice during the presentation session while a significant reduction of activation of the baso-lateral amygdala occurred in EC mice (ANOVA with repeated measurements followed by a SNK multiple range test: * denotes P<0.05, significantly different from SC group; univariate t-test: § denotes P<0.05 and §§ denotes P<0.01, significantly different from respective “control of presentation” animals (100%)). B. The novel object discrimination during the test session (24 h-ISI) was associated with a significant activation of the infralimbic cortex and the hippocampus in EC mice (univariate t-test: § denotes P<0.05, significantly different from respective “control of test” animals (100%)). Abbreviations: Fr, frontal cortex; PrL, prelimbic cortex; IL, infralimbic cortex; CgA, anterior cingulate cortex; Hpp, hippocampus; PRh, perirhinal cortex; BLA, amygdala, baso-lateral nucleus.
Figure 6
Figure 6. Microphotographs of brain c-Fos immunostaining related to the presentation and the test sessions.
During the presentation session, the number of c-Fos-positive cells counted in the hippocampus (represented here by the granular cell layer of the dentate gyrus), the perirhinal cortex and the baso-lateral amygdala was lower in EC mice compared to SC ones. By contrast, the number of c-Fos-positive cells counted in the hippocampus and the infralimbic cortex during the test session was higher in EC mice. The dark arrows indicate examples of nuclei showing c-Fos immunoreactivity. Unannotated scale bars: 50 µm.

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Marianne Leger is supported by funding from the French Ministry of Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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