期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：48
DOI：10.1073/pnas.2108534118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Sleep loss disrupts consolidation of hippocampus-dependent memory. To understand the cellular basis for this effect, we quantified RNAs associated with translating ribosomes in cytosol and on cellular membranes of different hippocampal neuron populations. Our analysis suggests that while sleep loss (but not learning) alters numerous ribosomal transcripts in cytosol, learning has dramatic effects on transcript profiles for less–well-characterized membrane-bound ribosomes. We demonstrate that postlearning sleep deprivation occludes already minimal learning-driven changes on cytosolic ribosomes. It simultaneously alters transcripts associated with metabolic and biosynthetic processes in membrane-bound ribosomes in excitatory hippocampal neurons and highly active, putative “engram” neurons, respectively. Together, these findings provide insights into the cellular mechanisms altered by learning and their disruption by subsequent sleep loss.
The hippocampus is essential for consolidating transient experiences into long-lasting memories. Memory consolidation is facilitated by postlearning sleep, although the underlying cellular mechanisms are largely unknown. We took an unbiased approach to this question by using a mouse model of hippocampally mediated, sleep-dependent memory consolidation (contextual fear memory). Because synaptic plasticity is associated with changes to both neuronal cell membranes (e.g., receptors) and cytosol (e.g., cytoskeletal elements), we characterized how these cell compartments are affected by learning and subsequent sleep or sleep deprivation (SD). Translating ribosome affinity purification was used to profile ribosome-associated RNAs in different subcellular compartments (cytosol and membrane) and in different cell populations (whole hippocampus, Camk2a+ neurons, or highly active neurons with phosphorylated ribosomal subunit S6 [pS6+
