Hippocampal and prefrontal contributions to memory-guided navigation depend on task epoch

Abstract

The hippocampus and medial prefrontal cortex (mPFC) are required for delayed working-memory tasks, but when in the task their engagement becomes necessary remains an open question. We trained mice on a delayed cue-guided T-maze navigation task and used transient optogenetic silencing to test the contribution of the mPFC and hippocampus during distinct task epochs. Surprisingly, silencing during the delay period did not impair performance. In contrast, perturbation during the early phase of the central arm traversal produced robust deficits. Mice made more perseverative choices, slowed their speed and ran farther down the track before turning towards the selected arm. Control experiments showed that these effects could not be explained by the manipulation targeting elapsed time and were rather specific to task phase. These results indicate that hippocampal and prefrontal contributions to memory-guided behavior are not uniform across the trial, but instead depend on task epoch. More broadly, they suggest that the functional engagement of these circuits is gated by behavioral state or context.