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

• 成果类型: Article
• 署名作者: Jun, Heechul; Lee, Jason Y.; Bleza, Nicholas R.; Ichii, Ayana; Donohue, Jordan D.; Igarashi, Kei M.
• 署名单位: University of California System; University of California Irvine; University of California System; University of California Irvine; University of California System; University of California Irvine; University of California System; University of California Irvine; University of California System; University of California Irvine
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6702
• DOI: 10.1038/s41586-024-07868-1
• 发表日期: 2024-09-12
• 关键词: hippocampal interactions; memory; cortex; network; REPRESENTATION; ORGANIZATION; signals; reward; cells; rats

摘要

The ability to learn novel items depends on brain functions that store information about items classified by their associated meanings and outcomes1-4, 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 (LECL5/6) 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 LECL5/6, developed an equivalent item-outcome rule map during learning. When LECL5/6 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, LECL5/6 representations of individual items were held completely separate, disrupting both learning and retrieval of associations. These results suggest that LECL5/6 neurons and mPFC neurons co-dependently encode item memory as a map of associated outcome rules.