Adult male C57BL/6J mice explored a familiar U-shaped track (F), then a similar novel one (N) differing only in local visuo-tactile cues, followed by a 2-h sleep or wake retention interval before re-exposure (N', F'). CA1 activity was monitored via miniscope Ca²⁺ imaging. Sleep, but not wakefulness, increased similarity of N' representations to F: F-N' cell-by-cell correlations 0.32±0.11 (sleep) vs 0.10±0.07 (wake), p=0.001, and a familiar-trained decoder predicted position in N' better after sleep (error 9.93±1.23 vs 11.23±0.64 cm, Mann-Whitney p=0.018) .
Critical caveat: the PV-based F-N' sleep-vs-wake comparison did not reach significance (paired t-test p=0.104) in the pooled trial set , so the representational effect rests mainly on cell-by-cell and decoding measures — a mixed result the abstract does not foreground.
Bilateral mPFC hM4Di silencing (DCZ 0.1 mg/kg) before sleep shifted hippocampal dynamics toward consolidation of the novel map: Generalization Index −0.08±0.05 (DCZ, n=4) vs 0.09±0.04 (sleep control, n=12) vs −0.05±0.05 (awake, n=8), Kruskal-Wallis p=0.0002, with DCZ statistically indistinguishable from wake (p=0.644) . Behaviorally, post-sleep N' re-exposure showed familiarity markers (speed 2.49±0.51 vs 1.72±0.66, p=0.005; stops 18.5±11.38 vs 37.42±22.04, p=0.007; n=12 trials, 7 mice) .
A minimal 10-neuron Hebbian network shows sleep-phase co-activation of F and N representations suffices to bias N' responses toward F — but the authors concede the actual instructive mPFC signal during sleep is unknown and was not modeled . This top-down framing complements established bottom-up sleep consolidation models and human EEG-fMRI work showing sleep-stage-dependent hippocampal–cortical coupling . Whether sleep promotes or limits generalization may depend on sleep stage: REM restriction drives fear overgeneralization in humans — a tension the paper does not address, since sleep was not staged.
What would falsify the central claim: a preregistered replication finding no F-N' similarity increase after sleep, or mPFC inactivation failing to reduce the Generalization Index. Confidence: moderate — internally consistent, well-controlled within-subject design, but small n and unverified sleep staging.
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