Biology subjects

Lyons, L. C.

Publications and source records attributed to Lyons, L. C..

4 recordsLinked to original sources

bioRxiv2025

Sleep deprivation selectively reactivates hippocampal CA1 pyramidal neurons.

Sleep supports a variety of physiological processes, ranging from metabolic to immune system homeostasis, and plays a critical role in cognition and memory. A brief period of sleep loss impairs memory, particularly hippocampus-dependent memories, and alters molecular signaling and synaptic plasticity in the hippocampus. Studies have shown that sleep deprivation (SD), alters neuronal activation as indicated by broad changes in gene expression signatures and by the altered expression of c-Fos, an immediate early gene that functions as a molecular marker of neuronal activity. In the present study, we examined hippocampal subregion-specific c-Fos induction patterns via immunohistochemical staining. We find that CA1 pyramidal neurons exhibit the most robust c-Fos induction after SD. Using an activity-driven ribosomal tagging system and a repeated SD model, we labeled sleep deprivation activated CA1 neurons and observed a population of excitatory neurons in area CA1 that are reactivated by repeated SD. Using the c-Fos-RiboTag system that enables the isolation of ribosomes attached mRNA from labeled neurons, we performed fosTRAP-seq and identified activity-dependent gene expression changes in c-Fos+ CA1 neurons. Our results revealed that synapse organization, protein dephosphorylation, cellular response to endogenous stimulus (such as insulin) are upregulated, whereas mRNA processing and splicing being downregulated. In summary, our study provides a detailed view of the activation of hippocampal neurons after SD, revealing a subset of CA1 pyramidal neurons that have higher sensitivity to the effect of sleep loss, shown as reactivation during repeated SD, allows investigation of molecular changes in neurons specifically impacted by repeated sleep loss. Our work uncovers a population of CA1 pyramidal neurons that are sensitive to repeated sleep loss and sheds light on a possible connection between acute and chronic sleep loss at the cellular and molecular levels. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/665413v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1cfa351org.highwire.dtl.DTLVardef@eb387dorg.highwire.dtl.DTLVardef@c9cf6forg.highwire.dtl.DTLVardef@1518b12_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Altered hippocampal transcriptome dynamics following sleep deprivation

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. These results clearly demonstrate that sleep deprivation differentially regulates gene expression on multiple transcriptomic levels to impact hippocampal function. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=180 HEIGHT=200 SRC="FIGDIR/small/445021v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1e611eborg.highwire.dtl.DTLVardef@1a26aa2org.highwire.dtl.DTLVardef@6e8e2org.highwire.dtl.DTLVardef@1a388f0_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Sleep modulates alcohol toxicity in Drosophila

Study ObjectivesAlcohol abuse is a significant public health problem, particularly in populations in which sleep deprivation is common as such as shift workers and aged individuals. Although research demonstrates the effect of alcohol on sleep, little is known about the role of sleep in alcohol sensitivity and toxicity. We investigated sleep as a factor modulating alcohol toxicity using Drosophila melanogaster, a model system ideal for studies of sleep, alcohol and aging. MethodsFollowing 24 hours of sleep deprivation using mechanical stimulation, Drosophila were exposed to binge-like alcohol exposures. Behavioral sensitivity, tolerance, and mortality were assessed. The effects of chronic sleep deprivation on alcohol toxicity were investigated using a short sleep mutant insomniac. Pharmacological induction of sleep for prior to alcohol exposure was accomplished using a GABAA-receptor agonist, 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) to determine if increased sleep mitigated the effects of alcohol toxicity on middle-aged flies and flies with environmentally disrupted circadian clocks mimicking groups more vulnerable to the effects of alcohol. ResultsAcute sleep deprivation increased alcohol-induced mortality following alcohol exposure. However, sleep deprivation had no effect on alcohol absorbance or clearance. Sleep deprivation also abolished functional tolerance measured 24 hours after the initial alcohol exposure, although tolerance at 4 h was observed. Pharmacologically increasing sleep prior to alcohol exposure decreased alcohol-induced mortality. ConclusionsSleep quantity prior to alcohol exposure affects alcohol toxicity with decreased sleep increasing alcohol toxicity and dampened 24-hour alcohol tolerance. In contrast, increased sleep mitigated alcohol-induced mortality even in vulnerable groups such as aging flies and those with circadian dysfunction. Statement of significanceWith the growing incidence of sleep deprivation and sleep disorders across adolescents and adults, it is important to understand the role of sleep in alcohol toxicity to develop future therapies for prevention and treatment of alcohol-induced pathologies. Using Drosophila melanogaster, an established model for both sleep and alcohol research, we found that acute and chronic sleep deprivation increased alcohol toxicity and eliminated long-term functional alcohol tolerance. In contrast, increased sleep prior to binge-like alcohol exposure mitigated alcohol-induced mortality even in vulnerable groups with higher susceptibility to alcohol toxicity.

neuroscience↗

bioRxiv2020

The CBP KIX domain regulates long-term memory and circadian activity

CREB-dependent transcription necessary for long-term memory is driven by interactions with CREB-binding protein (CBP), a multi-domain protein that binds numerous transcription factors. Identifying specific domain functions for multi-action proteins is essential to understand processes necessary for healthy living including cognitive function and a robust circadian clock. We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBPKIX/KIX mice with mutations that prevent phospho-CREB (Ser133) binding. We found that CBPKIX/KIX mice were impaired in long-term, but not short-term spatial memory in the Morris water maze. Using an unbiased analysis of gene expression after training for hippocampus-dependent memory, we discovered dysregulation of CREB and CLOCK target genes and downregulation of circadian genes in CBPKIX/KIX mice. With our finding that the CBP KIX domain was important for transcription of circadian genes, we profiled circadian activity in CBPKIX/KIX mice. CBPKIX/KIX mice exhibited delayed activity peaks after light offset and longer free-running periods in constant dark, although phase resetting to light was comparable to wildtype. These studies provide insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domain in vivo on circadian rhythms.

neuroscience↗