Qualitatively different hippocampal subfield engagement emerges with mastery of a spatial memory task by rats

The parallel, entorhinal cortex projections to different hippocampal regions potentially support separate mnemonic functions. To examine this possibility, rats were trained in a radial-arm maze task so that hippocampal activity could be compared after “early” (two sessions) or “late” (five sessions) learning. Induction of the immediate-early gene Zif268 was then measured, so revealing possible activity differences across hippocampal subfields andthe parahippocampal cortices. Each rat inthetwo experimental groups (early, late) was also yokedto a control ratthat obtainedthe same number of rewards, visitedthe same number of maze arms, and spent a comparable amount of time in the maze. Although overall Zif268 levels did not distinguish the four groups, significant correlations were found between spatial memory performance and levels of dentate gyrus Zif268 expression in the early but not the late training group. Conversely, hippocampalfields CA3 and CA1 Zif268 expression correlated with performance inthe late but notthe earlytraining group. This reversal inthe correlation pattern was echoed by structural equation modeling, which revealed dynamic changes in effective network connectivity.With early training,the dentate gyrus appearedto help determine CA1 activity, but by latetrainingthe dentate gyrus reduced its neural influence. Furthermore, CA1 was distinguished from CA3, each subfield developing opposite relations with task mastery. Thus, functional entorhinal cortex coupling with CA1 activity became more direct with additional training, so producing a trisynaptic circuit bypass. The present study reveals qualitatively different patterns of hippocampal subfield engagement dependent on task demands and mastery