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

Previous studies have highlighted an important role for hippocampal sharp-wave ripples in spatial alternation learning, as well as in modulating activity in the medial prefrontal cortex (mPFC). However, the direct influence of hippocampal sharp-wave ripples on mPFC activity during spatial alternation learning has not been investigated. Here, we train Long Evans rats on a three-arm radial maze to perform a sequence of alternations. Three alternation sequences needed to be learned, and while learning a 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 is 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.