Frontiers in Neuroscience (Nov 2023)

Homeostatic NREM sleep and salience network function in adult mice exposed to ethanol during development

  • Prachi Shah,
  • Aayush Kaneria,
  • Gloria Fleming,
  • Colin R. O. Williams,
  • Regina M. Sullivan,
  • Regina M. Sullivan,
  • Regina M. Sullivan,
  • Christian H. Lemon,
  • John Smiley,
  • John Smiley,
  • Mariko Saito,
  • Mariko Saito,
  • Donald A. Wilson,
  • Donald A. Wilson,
  • Donald A. Wilson

DOI
https://doi.org/10.3389/fnins.2023.1267542
Journal volume & issue
Vol. 17

Abstract

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Developmental exposure to ethanol is a leading cause of cognitive, emotional and behavioral problems, with fetal alcohol spectrum disorder (FASD) affecting more than 1:100 children. Recently, comorbid sleep deficits have been highlighted in these disorders, with sleep repair a potential therapeutic target. Animal models of FASD have shown non-REM (NREM) sleep fragmentation and slow-wave oscillation impairments that predict cognitive performance. Here we use a mouse model of perinatal ethanol exposure to explore whether reduced sleep pressure may contribute to impaired NREM sleep, and compare the function of a brain network reported to be impacted by insomnia–the Salience network–in developmental ethanol-exposed mice with sleep-deprived, saline controls. Mice were exposed to ethanol or saline on postnatal day 7 (P7) and allowed to mature to adulthood for testing. At P90, telemetered cortical recordings were made for assessment of NREM sleep in home cage before and after 4 h of sleep deprivation to assess basal NREM sleep and homeostatic NREM sleep response. To assess Salience network functional connectivity, mice were exposed to the 4 h sleep deprivation period or left alone, then immediately sacrificed for immunohistochemical analysis of c-Fos expression. The results show that developmental ethanol severely impairs both normal rebound NREM sleep and sleep deprivation induced increases in slow-wave activity, consistent with reduced sleep pressure. Furthermore, the Salience network connectome in rested, ethanol-exposed mice was most similar to that of sleep-deprived, saline control mice, suggesting a sleep deprivation-like state of Salience network function after developmental ethanol even without sleep deprivation.

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