Hierarchy in the mouse frontal cortex in mnemonic olfactory decision-making

The prefrontal cortex plays a critical role in integrating the memory of a recent experience to guide context-dependent decisions, yet how the finer, sub-steps of decision formation are physiologically implemented remains poorly understood. Using an olfactory delayed non-match-to-sample task with graded stimulus similarity in head-fixed mice, we examined how decisions emerge when a current sensory event and a memory of a recent event must be compared. With high-density extracellular recordings across the frontal cortex, we characterized odor-specific delay activity and decision-related signals. Interestingly, the secondary motor cortex showed minimal sensory coding, suggesting that areas engaged in mnemonic decision-making differ from those involved in simpler, stimulus-response decision-making in the rodent brain. Rather, there was a gradual emergence from sensory representations to choice-related activity, with intermediate regions showing choice modulations that retain stimulus sensitivity that arises with early timing, as well as balanced match vs. non-match selectivity. These results suggest that mnemonic decision-making is supported by a distributed frontal network in which sensory and choice signals are gradually integrated, rather than localized to a single comparator region.