Prefrontal neuronal ensembles link prior knowledge with novel actions during flexible action selection.

We make decisions based on currently perceivable information or an internal model of the environment. The medial prefrontal cortex (mPFC) and its interaction with the hippocampus have been implicated in the latter, model-based decision-making; however, the underlying computational properties remain incompletely understood. We have examined mPFC spiking and hippocampal oscillatory activity while rats flexibly select new actions using a known associative structure of environmental cues and outcomes. During action selection, the mPFC reinstates representations of the associative structure. These awake reactivation events are accompanied by synchronous firings among neurons coding the associative structure and those coding actions. Moreover, their functional coupling is strengthened upon the reactivation events leading to adaptive actions. In contrast, only cue-coding neurons improve functional coupling during hippocampal sharp wave ripples. Thus, the lack of direct experience disconnects the mPFC from the hippocampus to independently form self-organized neuronal ensemble dynamics linking prior knowledge with novel actions.