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To address the issue of how hippocampal neurons are involved into learning progress, we studied c-Fos expression in rat hippocampal subfields at different stages of appetitive instrumental learning. To model the first stage of learning, we pre-trained animals to approach the lever to obtain the food, and then made this behavior ineffective by not reinforcing it during the last session (“mismatch” group). Another group just acquired lever-pressing behavior at that day (“acquisition” group). Animals of the third group performed this well-trained behavior (“performance” group). The number of Fos-positive neurons in all hippocampal regions of the “mismatch” group animals was higher than in the ones of the home cage control group animals. The number of Fos-positive neurons was increased in CA1 and CA3 areas, but not in the dentate gyrus of both the “acquisition” and “performance” group animals as compared with the control group. We also found segmented c-Fos expression, which was more evident in “acquisition” group animals. Thus, our results suggest that during the first (mismatch) stage of learning hippocampal neurons are activated in an equally distributed manner. The following clustered pattern of activated CA1 neurons during the acquisition stage may reflect specialization of these neurons in respect to the specific lever-pressing behavior.

Clustered c-Fos Activation in Rat Hippocampus at the Acquisition Stage of Appetitive Instrumental Learning