Differential Cortical c-Fos and Zif-268 Expression after Object and Spatial Memory Processing in a Standard or Episodic-Like Object Recognition Task

Abstract

Episodic memory reflects the capacity to recollect what, where, and when a specific event happened in an integrative manner. Animal studies have suggested that the medial temporal lobe and the medial pre-frontal cortex are important for episodic-like memory (ELM) formation. The goal of present study was to evaluate whether there are different patterns of expression of the immediate early genes c-Fos and Zif-268 in these cortical areas after rats are exposed to object recognition (OR) tasks with different cognitive demands. Male rats were randomly assigned to five groups: home cage control, empty open field (CTR-OF), open field with one object (CTR-OF + Obj), novel OR task, and ELM task and were killed 1 h after the last behavioral procedure. Rats were able to discriminate the objects in the OR task. In the ELM task, rats showed spatial (but not temporal) discrimination of the objects. We found an increase in the c-Fos expression in the dorsal dentate gyrus (DG) and in the perirhinal cortex (PRh) in the OR and ELM groups. The OR group also presented an increase of c-Fos expression in the medial prefrontal cortex (mPFC). Additionally, the OR and ELM groups had increased expression of Zif-268 in the mPFC. Moreover, Zif-268 was increased in the dorsal CA1 and PRh only in the ELM group. In conclusion, the pattern of activation was different in tasks with different cognitive demands. Accordingly, correlation tests suggest the engagement of different neural networks in the tasks used. Specifically, perirhinal-DG co-activation was detected after the what-where memory retrieval, but not after the novel OR task. Both regions correlated with the respective behavioral outcome. These findings can be helpful in the understanding of the neural networks underlying memory tasks with different cognitive demands.

Keywords: episodic memory; hippocampus; immediate early genes; plasticity; recognition memory; spatial memory.

Figure 1

Experimental procedure. CTR-HC, home cage control (without behavioral sessions); CTR-OF, open field control (four expositions to the empty open field); CTR-OF + Obj, open field + object control (exposition to an object in the last behavioral session); OR, object recognition task (discrimination between novel and familiar objects); ELM, episodic-like memory task (spatiotemporal discrimination of familiar objects).

Figure 2

Exploration ratios (mean + SEM) within the initial 2 min of the test session of the object recognition task. *p < 0.05 compared to old objects exploration (paired samplest-test).

Figure 3

Exploration ratios (mean ± SEM) within 5 min of the test session of the episodic-like memory (ELM) task. Objects: A1, stationary old familiar; A2, displaced old familiar; B1, stationary recent familiar; and B2, displaced recent familiar. *p < 0.05 compared to A1 (paired two-tailedt-test).

Figure 4

Expression of c-Fos in different brain areas (HP, hippocampus; DG, dentate gyrus; CA1; CA3; mPFC, medial prefrontal cortex; V1, visual area 1; ERH, entorhinal cortex; PRh, perirhinal cortex) for home cage control (CTR-HC), open-field control (CTR-OF), open-field + object control (CRT-OF + Obj), object recognition (OR), and episodic-like memory (ELM) groups. The normalized number of cells is expressed as the mean ± SEM. *p < 0.05 compared to CTR-HC and CTR-OF; ^#p < 0.05 compared to CTR-OF + Obj; °p < 0.05 compared to OR (one-way ANOVA followed by Tukey’s test).

Figure 5

Representative images of c-Fos expression in dentate gyrus (DG) and medial prefrontal cortex (mPFC) from subjects of control open-field + object (CTRL-OF + Obj), novel object recognition (OR), and episodic-like memory (ELM) task groups.

Figure 6

Expression of Zif-268 in different brain areas (HP, hippocampus; DG, dentate gyrus; CA1; CA3; mPFC, medial prefrontal cortex; V1, visual area 1; ERH, entorhinal cortex; PRh, perirhinal cortex) for home cage control (CTR-HC), open-field control (CTR-OF), open-field + object control (CRT-OF + Obj), object recognition (OR) episodic-like memory (ELM) task groups. The normalized number of cells is expressed as the mean ± SEM. *p < 0.05 compared to CTR-HC and CTR-OF; ^#p < 0.05 compared to CTR-OF + Obj; °p < 0.05 compared to OR (one-way ANOVA followed by Tukey’s test).

Figure 7

Representative images of Zif-268 expression in CA1 hippocampal subregion and perirhinal cortex (PRh) from subjects of control open-field + object (CTRL-OF + Obj), novel object recognition (OR), and episodic-like memory (ELM) task groups.