Sleep-dependent engram reactivation during hippocampal memory consolidation associated with subregion-specific biosynthetic changes.

Post-learning sleep is essential for hippocampal memory processing, including contextual fear memory consolidation. We labeled context-encoding engram neurons in the hippocampal dentate gyrus (DG) and assessed reactivation of these neurons after fear learning. Post-learning sleep deprivation (SD) selectively disrupted reactivation of inferior blade DG engram neurons, linked to SD-induced suppression of neuronal activity in the inferior, but not superior DG blade. Subregion-specific spatial profiling of transcripts revealed that transcriptomic responses to SD differed greatly between hippocampal CA1, CA3, and DG inferior blade, superior blade, and hilus. Activity-driven transcripts, and those associated with cytoskeletal remodeling, were selectively suppressed in the inferior blade. Critically, learning-driven transcriptomic changes differed dramatically between the DG blades and were absent from all other regions. Together, these data suggest that the DG is critical for sleep-dependent memory consolidation, and that the effects of sleep loss on the hippocampus are highly subregion-specific.

Fatigue and Quality of Life in Children with Hearing Loss or Obstructive Sleep Apnea.

OBJECTIVE: To investigate the fatigue levels of children with hearing loss (HL) and obstructive sleep apnea (OSA), hypothesizing that the fatigue experienced by children with HL is under-recognized. STUDY DESIGN: Cross-sectional survey. METHODS: We identified children aged 2-18 with HL, OSA, sleep-disordered breathing (SDB), and controls from a pediatric otolaryngology clinic and sleep center. Children and/or parents completed the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL MFS), Hearing Environments And Reflection on Quality of Life (HEAR-QL), and OSA-18. RESULTS: Responses of 50 children with HL, 79 with OSA, and 18 with SDB were compared with those of 49 recruited controls (RC) and literature controls (LC). Children with HL or OSA had higher fatigue than controls in the PedsQL MFS self-reported (HL 65.4, OSA 54.7, RC 71.8, LC 80.5, p < 0.001) and parent-reported (HL 64.6, OSA 59.3, RC 75.2, LC 89.6, p < 0.001). Children with HL had Cognitive Fatigue similar to that of children with OSA (self 60.4 vs. 49.5, p = 0.170; parent 56.0 vs. 56.7, p = 0.998), though with decreased Sleep/Rest Fatigue (self 67.8 vs. 56.3, p = 0.033; parent 69.8 vs. 57.5, p = 0.001). Children with HL or OSA had lower disease-related quality of life (QOL) than controls in the HEAR-QL and OSA-18, respectively. Stratification with disease severity revealed no differences in fatigue. CONCLUSION: Children with HL or OSA experience higher fatigue and lower QOL than controls. Similar Cognitive Fatigue in both groups suggests under-recognized fatigue in children with HL. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:443-451, 2024.

Causal role for sleep-dependent reactivation of learning-activated sensory ensembles for fear memory consolidation.

Learning-activated engram neurons play a critical role in memory recall. An untested hypothesis is that these same neurons play an instructive role in offline memory consolidation. Here we show that a visually-cued fear memory is consolidated during post-conditioning sleep in mice. We then use TRAP (targeted recombination in active populations) to genetically label or optogenetically manipulate primary visual cortex (V1) neurons responsive to the visual cue. Following fear conditioning, mice respond to activation of this visual engram population in a manner similar to visual presentation of fear cues. Cue-responsive neurons are selectively reactivated in V1 during post-conditioning sleep. Mimicking visual engram reactivation optogenetically leads to increased representation of the visual cue in V1. Optogenetic inhibition of the engram population during post-conditioning sleep disrupts consolidation of fear memory. We conclude that selective sleep-associated reactivation of learning-activated sensory populations serves as a necessary instructive mechanism for memory consolidation.