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Altered hippocampal transcriptome dynamics following sleep deprivation.

ABSTRACT: Widespread sleep deprivation is a continuing public health problem in the United States and worldwide affecting adolescents and adults. Acute sleep deprivation results in decrements in spatial memory and cognitive impairments. The hippocampus is vulnerable to acute sleep deprivation with changes in gene expression, cell signaling, and protein synthesis. Sleep deprivation also has long lasting effects on memory and performance that persist after recovery sleep, as seen in behavioral studies from invertebrates to humans. Although previous research has shown that acute sleep deprivation impacts gene expression, the extent to which sleep deprivation affects gene regulation remains unknown. Using an unbiased deep RNA sequencing approach, we investigated the effects of acute sleep deprivation on gene expression in the hippocampus. We identified 1,146 genes that were significantly dysregulated following sleep deprivation with 507 genes upregulated and 639 genes downregulated, including protein coding genes and long non-coding RNAs not previously identified as impacted by sleep deprivation. Notably, genes significantly upregulated after sleep deprivation were associated with RNA splicing and the nucleus. In contrast, downregulated genes were associated with cell adhesion, dendritic localization, the synapse, and postsynaptic membrane. Furthermore, we found through independent experiments analyzing a subset of genes that three hours of recovery sleep following acute sleep deprivation was sufficient to normalize mRNA abundance for most genes, although exceptions occurred for some genes that may affect RNA splicing or transcription. These results clearly demonstrate that sleep deprivation differentially regulates gene expression on multiple transcriptomic levels to impact hippocampal function.

SUBMITTER: Gaine ME

PROVIDER: S-EPMC8361790 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Study objectivesTemporal expectation enables us to focus limited processing resources, thereby optimizing perceptual and motor processing for critical upcoming events. We investigated the effects of total sleep deprivation (TSD) on temporal expectation by evaluating the foreperiod and sequential effects during a psychomotor vigilance task (PVT). We also examined how these two measures were modulated by vulnerability to TSD.DesignThree 10-min visual PVT sessions using uniformly distributed foreperiods were conducted in the wake-maintenance zone the evening before sleep deprivation (ESD) and three more in the morning following approximately 22 h of TSD. TSD vulnerable and nonvulnerable groups were determined by a tertile split of participants based on the change in the number of behavioral lapses recorded during ESD and TSD. A subset of participants performed six additional 10-min modified auditory PVTs with exponentially distributed foreperiods during rested wakefulness (RW) and TSD to test the effect of temporal distribution on foreperiod and sequential effects.SettingSleep laboratory.ParticipantsThere were 172 young healthy participants (90 males) with regular sleep patterns. Nineteen of these participants performed the modified auditory PVT.Measurements and resultsDespite behavioral lapses and slower response times, sleep deprived participants could still perceive the conditional probability of temporal events and modify their level of preparation accordingly. Both foreperiod and sequential effects were magnified following sleep deprivation in vulnerable individuals. Only the foreperiod effect increased in nonvulnerable individuals.ConclusionsThe preservation of foreperiod and sequential effects suggests that implicit time perception and temporal preparedness are intact during total sleep deprivation. Individuals appear to reallocate their depleted preparatory resources to more probable event timings in ongoing trials, whereas vulnerable participants also rely more on automatic processes.

Project description:Study objectivesSleep rebound-the increase in sleep that follows sleep deprivation-is a hallmark of homeostatic sleep regulation that is conserved across the animal kingdom. However, both the mechanisms that underlie sleep rebound and its relationship to habitual daily sleep remain unclear. To address this, we developed an efficient thermogenetic method of inducing sleep deprivation in Drosophila that produces a substantial rebound, and applied the newly developed method to assess sleep rebound in a screen of 1,741 mutated lines. We used data generated by this screen to identify lines with reduced sleep rebound following thermogenetic sleep deprivation, and to probe the relationship between habitual sleep amount and sleep following thermogenetic sleep deprivation in Drosophila.MethodsTo develop a thermogenetic method of sleep deprivation suitable for screening, we thermogenetically stimulated different populations of wake-promoting neurons labeled by Gal4 drivers. Sleep rebound following thermogenetically-induced wakefulness varies across the different sets of wake-promoting neurons that were stimulated, from very little to quite substantial. Thermogenetic activation of neurons marked by the c584-Gal4 driver produces both strong sleep loss and a substantial rebound that is more consistent within genotypes than rebound following mechanical or caffeine-induced sleep deprivation. We therefore used this driver to induce sleep deprivation in a screen of 1,741 mutagenized lines generated by the Drosophila Gene Disruption Project. Flies were subjected to 9 h of sleep deprivation during the dark period and released from sleep deprivation 3 h before lights-on. Recovery was measured over the 15 h following sleep deprivation. Following identification of lines with reduced sleep rebound, we characterized baseline sleep and sleep depth before and after sleep deprivation for these hits.ResultsWe identified two lines that consistently exhibit a blunted increase in the duration and depth of sleep after thermogenetic sleep deprivation. Neither of the two genotypes has reduced total baseline sleep. Statistical analysis across all screened lines shows that genotype is a strong predictor of recovery sleep, independent from effects of genotype on baseline sleep.ConclusionsOur data show that rebound sleep following thermogenetic sleep deprivation can be genetically separated from sleep at baseline. This suggests that genetically controlled mechanisms of sleep regulation not manifest under undisturbed conditions contribute to sleep rebound following thermogenetic sleep deprivation.

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Altered hippocampal transcriptome dynamics following sleep deprivation.

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