Prefrontal coding of learned and inferred knowledge during REM & NREM sleep

Abstract

Idling brain activity has been proposed to facilitate inference, insight, and innovative problem-solving1-4. However, it remains unclear how and when the subconscious brain can create novel ideas. Here, we show coordinated roles of non-rapid eye movement (NREM) and rapid-eye movement (REM) sleep in weaving inferential information from learned information. In a transitive inference paradigm, mice gained the inference one day, but not shortly, after complete training. Inhibiting the neuronal computations in the anterior cingulate cortex (ACC) during post-learning either NREM or REM sleep, but not wakefulness, disrupted the inference without affecting the learned knowledge. In vivo Ca2+ imaging showed gradual development of inference-related representation, peaking at post-training REM sleep. Neurons representing learned information co-reactivated significantly during post-training NREM sleep, while their co-reactivation with neurons representing inferential information was significantly higher during REM sleep. Furthermore, after insufficient learning, artificial activation of medial entorhinal cortex-ACC dialogue during only REM sleep created inferential knowledge. These findings suggest that NREM sleep organizes the scattered learned knowledge in a complete hierarchy, while REM sleep computes the inferential information from the organized hierarchy. Collectively, our study provides a mechanistic insight on NREM and REM coordination in weaving inferential knowledge, thus highlighting the power of idling brain in cognitive flexibility.