Emergence of spatial behavioral function and associated mossy fiber connectivity and c-Fos labeling patterns in the hippocampus of rats.

Improvement on spatial tasks is observed during a late, postnatal developmental period (PND18 - PND24).  The purpose of the current work was 1) to determine whether the emergence of spatial-behavioral function was based on the ability to generate appropriate behavioral output; 2) to assess whether mossy fiber connectivity patterns preceded the emergence of spatial-behavioral function; 3) to explore functional changes in the hippocampus to determine whether activity in hippocampal networks occurred in a training-dependent or developmentally-dependent fashion.  To these ends, male, Long Evans rats were trained on a spatial water or dry maze task for one day (PND16, PND18 or PND20) then euthanized.  Training on these 2 tasks with opposing behavioral demands (swimming versus exploration) was hypothesized to control for behavioral topology.  Only at PND20 was there evidence of spatial-behavioral function for both tasks.  Examination of synaptophysin staining in the CA3 region (i.e., mossy fiber projections) revealed enhanced connectivity patterns that preceded the emergence of spatial behavior.  Analysis of c-Fos labeling (functional changes) revealed developmentally-dependent increases in c-Fos positive cells in the dentate gyrus, CA3 and CA1 regions whereas training-dependent increases were noted in the CA3 and CA1 regions for the water-maze trained groups.  Results suggest that changes in mossy fiber connectivity in association with enhanced hippocampal functioning precede the emergence of spatial behavior observed at PND20.  The combination of neuroanatomical and behavioural results confirms the hypothesis that this time represents a sensitive period for hippocampal development and modification and the emergence of spatial/ cognitive function.

Enhanced adolescent learning and hippocampal axonal projections following preadolescent spatial exposure to a water or dry maze.

The present work sought to determine whether preadolescent exposure to a different task in the same spatial environment would lead to enhancement of water-maze performance and changes in hippocampal connectivity. Separate groups of preadolescent (p16-p26) Long Evans rats (LER) were exposed to the same room and arena using either a water-maze (WM) or a dry-maze (DM), while a third group received no exposure to the spatial cues (NT) but were handled. Three weeks later, rats were tested on the WM or DM task in the same room where preadolescent exposure took place. This set up conditions where the DM/WM and WM/DM groups were exposed to the same spatial cues during the preadolescent and adolescent (p40-p44) phases but performed different tests allowing for the dissociation of spatial cue exposure and task familiarity on adolescent performance. When animals experienced similar preadolescent and adolescent conditions (WM/WM or DM/DM), there was improved performance over animals with no preadolescent spatial exposure (NT/WM or NT/DM). In group DM/WM, there was enhanced adolescent performance compared to group NT/WM. In contrast, group WM/DM did not show enhanced adolescent performance. Compared to groups with no preadolescent spatial exposure, groups with both preadolescent and adolescent spatial exposure showed elevated synaptophysin staining in the hippocampal CA3 region indicating an expanded axonal projection in this region. These data suggest the possibility that exposure to spatial cues during the preadolescent period, independent from task-specific requirements, contributes to enhanced adolescent spatial performance on the WM. This appears to be linked with the reorganization of axonal inputs to the CA3 region.