Prefrontal and lateral entorhinal neurons co-dependently learn item-outcome rules.

The ability to learn novel items depends on brain functions that store information about items classified by their associated meanings and outcomes, but the underlying neural circuit mechanisms of this process remain poorly understood. Here we show that deep layers of the lateral entorhinal cortex (LEC) contain two groups of 'item-outcome neurons': one developing activity for rewarded items during learning, and another for punished items. As mice learned an olfactory item-outcome association, we found that the neuronal population of LEC layers 5/6 (LEC) formed an internal map of pre-learned and novel items, classified into dichotomic rewarded versus punished groups.