Sharp-wave ripple associated activity in the medial prefrontal cortex supports spatial rule switching

Abstract

Previous studies have highlighted an important role for hippocampal sharp-wave ripples in spatial alternation learning, as well as modulating activity in the medial prefrontal cortex (mPFC). However, no study so far has investigated the direct influence of hippocampal sharp-wave ripples on mPFC activity during spatial alternation learning. Long Evans rats were trained on a three-arm radial maze to perform a sequence of alternations. Three different alternation sequences needed to be learnt, and while learning a new sequence, the activity in the mPFC was inhibited either directly following sharp-wave ripples in the hippocampus (on-time condition) or with a randomized delay (delayed condition). In the on-time condition the behavioral performance was significantly worse compared to the same animals in the delayed inhibition condition, as measured by a lower correct alternation performance and more perseverative behavior. This indicates that the activity in the mPFC directly following hippocampal sharp-wave ripples is necessary for spatial rule switching.