The Emergence of New Schema Memory Requires Sleep

Schema memory refers to generalized knowledge that is formed across multiple episodes containing regularities. Schema memory is thought to be formed in an active systems consolidation process that transforms individual episodic representations into neocortically anchored schema representations and that is facilitated by sleep. Here we show in rats that sleep is indeed critical for the emergence of a new schema memory. Male rats (<i>n</i> = 20) were trained on an elaborated version of the object-place recognition task, which allowed for abstraction of a spatial rule across eight encoding episodes spaced 20 min apart without intermittent sleep. During each episode, animals freely explored two objects in an open-field arena. Following the encoding phase, animals either slept or were kept awake for 2 h, after which they remained undisturbed for 22 h before schema memory for the spatial rule was assessed. Only animals that slept during the 2 h postencoding window exhibited schema memory. Prior knowledge conflicting with the spatial rule prevented schema memory formation. c-Fos expression assessed at retrieval indicated that successful schema recall was supported by a more sparsely activated yet highly interconnected network comprising, among others, the medial prefrontal cortex and hippocampus. Our findings highlight the critical role of immediate postencoding sleep in forming new spatial schema memory.