The Development of Spatial Memory Processes and Associated Cellular Correlates in Juvenile Rats

The late postnatal period is marked by neurodevelopmental changes, from gross morphological alterations to finite cellular and molecular variations. The hippocampus is one such structure that undergoes extensive morphological and cytological remodeling during the juvenile period, which is thought to mediate the maturation of cognitive processing. Hippocampal remodeling leads to the strengthening of intra-hippocampal and hippocampal-cortical connectivity, allowing for the consolidation of information into remote stores within extrahippocampal regions. A link between changes in the duration of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAr)-mediated synaptic responses in the hippocampus and the emergence of spatial navigation has been shown. AMPAr are made up of 4 subunits, of which GluR1 and GluR2 have been shown to play the most prominent role in cognitive processes. The current thesis investigated whether preadolescent spatial memories acquired during this period of hippocampal synaptic modification persist beyond 24 hours and stabilize into the postadolescent period. We further aimed to identify the neural correlates thought to underlie the emergence of such processes, while determining training factors that may facilitate spatial memory processing. To this extent, rats were trained on spatial memory tasks during the period of hippocampal remodeling and assessed at either recent (24h) or remote (3 week) testing intervals. Their performance on the tasks was compared to adults in order to delineate the developmental period in which memory processing in juveniles resembles that in adults. c-Fos immunohistochemistry was performed on both the hippocampus and anterior cingulate cortex (ACC) in order to determine their contributions to testing performance at either interval, while Western blotting in both regions identified GluR1 and GluR2 levels following testing. Results indicated that the emergence of recent memory processing coincided with the initial onset of hippocampal remodeling, while remote memory processes showed a protracted development, manifesting during late-phase hippocampal remodeling. The pattern of memory consolidation suggests that the hippocampus is initially responsible for the processing of recently acquired information, after which it is stabilized and consolidated into remote stores within the ACC, rendering it independent of hippocampal activity. Both recent and remote memory processing are likely mediated by the development of synaptic components, particularly GluR1 and GluR2.