Differential learning-stage dependent patterns of c-Fos protein expression in brain regions during the acquisition and memory consolidation of an operant task in mice.

The present study analysed the effects of the stage of learning of an appetitive operant conditioning task on the spatial and temporal patterns of c-Fos protein levels in the brain of BALB/c mice. c-Fos levels were assessed by immunohistochemistry at either 60, 120 or 180 min after either the first, the second or the fifth daily training session and compared to sham animals. The results show an increase of c-Fos-positive nuclei in several subcortical and cortical brain regions, 60-min post-acquisition. Because these activations were a function of task mastery, the data indicate that they were specifically related to learning. Following the first acquisition session, significant increases in c-Fos-positive neurons were observed in the dorsal hippocampus (CA3), anterior cingulate, occipital and parietal cortices. Following the second daily training session, c-Fos was highly expressed in some subcortical regions, the hippocampus, the subiculum, the entorhinal, and posterior cingulate areas. Moreover, a significant correlation was found between the progression of performance from day 1 to day 2 and c-Fos expression on the hippocampal CA1 subfield. Following complete acquisition, no further task-dependent increases in c-Fos-labelled nuclei was observed in any brain region sampled, suggesting that the intervention of c-Fos-induced mechanisms in the consolidation process were terminated. The training stage-dependent changes in regional post-training c-Fos expression in the hippocampus and the connected limbic regions suggest that this neuronal network is actively engaged in memory consolidation processes.