Department of Anatomy and Neurobiology, School of Medicine, University of California Irvine, Irvine, CA, USA.
Department of Biomedical Engineering, Samueli School of Engineering, University of California Irvine, Irvine, CA, USA.
Nature. 2024 Sep;633(8031):864-871. doi: 10.1038/s41586-024-07868-1. Epub 2024 Aug 21.
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. Neurons in the medial prefrontal cortex (mPFC), which form a bidirectional loop circuit with LEC, developed an equivalent item-outcome rule map during learning. When LEC 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 representations of individual items were held completely separate, disrupting both learning and retrieval of associations. These results suggest that LEC 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的功能，这些功能存储了与事物相关的意义和结果的信息，但这一过程的潜在神经回路机制仍知之甚少。在这里，我们发现外侧内嗅皮层（LEC）的深层包含两组“项目-结果神经元”：一组在学习过程中对奖励项目产生活动，另一组对惩罚项目产生活动。当老鼠学习嗅觉项目-结果关联时，我们发现 LEC 层 5/6（LEC）的神经元群体形成了一个预先学习和新物品的内部图谱，分为二分的奖励和惩罚组。与 LEC 形成双向环路的内侧前额叶皮层（mPFC）中的神经元在学习过程中形成了一个等价的项目-结果规则图谱。当 LEC 神经元被光遗传抑制时，新的 mPFC 神经元的代表无法将新的项目分成奖励和惩罚组，从而损害了老鼠的新学习。相反，当 mPFC 神经元被抑制时，LEC 神经元对个别项目的表示则完全分开，从而破坏了联想的学习和检索。这些结果表明，LEC 神经元和 mPFC 神经元共同依赖于将项目记忆编码为关联结果规则的图谱。
