Unfolding of spatial representation at systems level in infant rats

Spatial representations enable navigation from early life on. However, the brain regions essential to form spatial representations, like the hippocampus, are considered functionally immature before weaning. Here, we examined the formation of representations of space in rat pups on postnatal day (PD) 16, using a simple habituation paradigm where the pups were exposed to an arena on three occasions, separated by ~140 min. Whereas on the first two occasions the arena was the same, on the third "test" occasion either proximal cues (Prox group), or distal cues (Dist group), or proximal and distal cues (Prox-Dist group), or no cues (No-change group) were rearranged. Locomotion (distance traveled) was used as behavioral measure of habituation, and c-Fos expression to measure regional brain activity at test. Locomotion generally decreased across the first two occasions. At test, it reached a minimum in the No-change group, indicating familiarity with the spatial conditions. By contrast, the Prox-Dist group displayed a significant increase in locomotion which was less robust in the Prox group and absent in the Dist group, a pattern suggesting that the pups relied more on proximal than distal cues during spatial exploration. c-Fos activity in the No-change group was significantly suppressed in the hippocampus (CA1, CA3, dentate gyrus) but simultaneously enhanced in the prelimbic area (PL) of the medial prefrontal cortex, compared with untreated Home-cage controls, pointing to a possible involvement of the PL in regulating locomotion in familiar spaces. By contrast, in both Prox-Dist and Prox groups c-Fos activity was enhanced in hippocampal CA1 and CA3 regions, suggesting these regions might be particularly involved in regulating exploration of spatial novelty. Our findings show that functional representations of space at a systems level are formed already in pre-weanling rats.