Medial Prefrontal Cortex Population Activity Is Plastic Irrespective of Learning

The prefrontal cortex (PFC) is thought to learn the relationships between actions and their outcomes. But little is known about what changes to population activity in PFC are specific to learning these relationships. Here we characterize the plasticity of population activity in the medial PFC (mPFC) of male rats learning rules on a Y-maze. First, we show that the population always changes its patterns of joint activity between the periods of sleep either side of a training session on the maze, regardless of successful rule learning during training. Next, by comparing the structure of population activity in sleep and training, we show that this population plasticity differs between learning and nonlearning sessions. In learning sessions, the changes in population activity in post-training sleep incorporate the changes to the population activity during training on the maze. In nonlearning sessions, the changes in sleep and training are unrelated. Finally, we show evidence that the nonlearning and learning forms of population plasticity are driven by different neuron-level changes, with the nonlearning form entirely accounted for by independent changes to the excitability of individual neurons, and the learning form also including changes to firing rate couplings between neurons. Collectively, our results suggest two different forms of population plasticity in mPFC during the learning of action-outcome relationships: one a persistent change in population activity structure decoupled from overt rule-learning, and the other a directional change driven by feedback during behavior.SIGNIFICANCE STATEMENT The PFC is thought to represent our knowledge about what action is worth doing in which context. But we do not know how the activity of neurons in PFC collectively changes when learning which actions are relevant. Here we show, in a trial-and-error task, that population activity in PFC is persistently changing, regardless of learning. Only during episodes of clear learning of relevant actions are the accompanying changes to population activity carried forward into sleep, suggesting a long-lasting form of neural plasticity. Our results suggest that representations of relevant actions in PFC are acquired by reward imposing a direction onto ongoing population plasticity.