The ability to learn novel items depends on brain functions that store information about items classified by their associated meanings and outcomes^1,2,3,4, 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_L5/6) formed an internal map of pre-learned and novel items, classified into dichotomic rewarded versus punished groups. Neurons in the medial prefrontal cortex (mPFC), which form a bidirectional loop circuit with LEC_L5/6, developed an equivalent item–outcome rule map during learning. When LEC_L5/6 neurons were optogenetically inhibited, tangled mPFC representations of novel items failed to split into rewarded versus punished groups, impairing new learning by mice. Conversely, when mPFC neurons were inhibited, LEC_L5/6 representations of individual items were held completely separate, disrupting both learning and retrieval of associations. These results suggest that LEC_L5/6 neurons and mPFC neurons co-dependently encode item memory as a map of associated outcome rules.

学习新事物的能力取决于大脑功能，这些功能存储有关按相关含义和结果分类的项目的信息^1,2,3,4 ，但这一过程的潜在神经回路机制仍然知之甚少。在这里，我们表明，外侧内嗅皮层（LEC）的深层包含两组“项目-结果神经元”：一组在学习过程中为奖励项目开发活动，另一组为惩罚项目开发活动。当小鼠学习嗅觉项目-结果关联时，我们发现 LEC 5/6 层 (LEC _L5/6 ) 的神经元群形成了预先学习的和新项目的内部图，分为奖励组和惩罚组。内侧前额皮质 (mPFC) 中的神经元与 LEC _L5/6形成双向环路，在学习过程中开发出等效的项目-结果规则图。当 LEC _L5/6神经元受到光遗传学抑制时，新事物的纠结的 mPFC 表征无法分为奖励组和惩罚组，从而损害了小鼠的新学习能力。相反，当 mPFC 神经元受到抑制时，各个项目的 LEC _L5/6表示完全分开，从而破坏关联的学习和检索。这些结果表明 LEC _L5/6神经元和 mPFC 神经元共同依赖地将项目记忆编码为相关结果规则的映射。