Learning differentially shapes prefrontal and hippocampal activity during classical conditioning.

The ability to use sensory cues to inform goal-directed actions is a critical component of behavior. To study how sounds guide anticipatory licking during classical conditioning, we employed high-density electrophysiological recordings from the hippocampal CA1 area and the prefrontal cortex (PFC) in mice. CA1 and PFC neurons undergo distinct learning-dependent changes at the single-cell level and maintain representations of cue identity at the population level. In addition, reactivation of task-related neuronal assemblies during hippocampal awake Sharp-Wave Ripples (aSWRs) changed within individual sessions in CA1 and over the course of multiple sessions in PFC. Despite both areas being highly engaged and synchronized during the task, we found no evidence for coordinated single cell or assembly activity during conditioning trials or aSWR. Taken together, our findings support the notion that persistent firing and reactivation of task-related neural activity patterns in CA1 and PFC support learning during classical conditioning.