Sleep loss disrupts Arc expression in dentate gyrus neurons

James E Delorme,Sara J Aton,Varna Kodoth

doi:10.1016/j.nlm.2018.04.006

James E Delorme, Sara J Aton + Show 1 more

Open Access

https://doi.org/10.1016/j.nlm.2018.04.006

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Abstract

Sleep loss affects many aspects of cognition, and memory consolidation processes occurring in the hippocampus seem particularly vulnerable to sleep loss. The immediate-early gene Arc plays an essential role in both synaptic plasticity and memory formation, and its expression is altered by sleep. Here, using a variety of techniques, we have characterized the effects of brief (3-h) periods of sleep vs. sleep deprivation (SD) on the expression of Arc mRNA and Arc protein in the mouse hippocampus and cortex. By comparing the relative abundance of mature Arc mRNA with unspliced pre-mRNA, we see evidence that during SD, increases in Arc across the cortex, but not hippocampus, reflect de novo transcription. Arc increases in the hippocampus during SD are not accompanied by changes in pre-mRNA levels, suggesting that increases in mRNA stability, not transcription, drives this change. Using in situ hybridization (together with behavioral observation to quantify sleep amounts), we find that in the dorsal hippocampus, SD minimally affects Arc mRNA expression, and decreases the number of dentate gyrus (DG) granule cells expressing Arc. This is in contrast to neighboring cortical areas, which show large increases in neuronal Arc expression after SD. Using immunohistochemistry, we find that Arc protein expression is also differentially affected in the cortex and DG with SD - while larger numbers of cortical neurons are Arc+, fewer DG granule cells are Arc+, relative to the same regions in sleeping mice. These data suggest that with regard to expression of plasticity-regulating genes, sleep (and SD) can have differential effects in hippocampal and cortical areas. This may provide a clue regarding the susceptibility of performance on hippocampus-dependent tasks to deficits following even brief periods of sleep loss.

Highlights

IntroductionNumerous studies have shown that following memory encoding, sleep promotes information storage in the brain
Over the past century, numerous studies have shown that following memory encoding, sleep promotes information storage in the brain
Using these primers (Fig. 1A) we found no significant effect of sleep deprivation (SD) on hippocampal Arc pre-mRNA levels (Fig. 1B), which were nearly identical in sleep in their home cage (Sleep) and SD mice (Sleep = 1.07 ± 0.20 vs. SD = 1.10 ± 0.07, N.S., Student’s t-test)

Summary

Introduction

Numerous studies have shown that following memory encoding, sleep promotes information storage in the brain. This has led to numerous theories of how sleep could facilitate plasticity of synapses between neurons involved in memory formation (Puentes-Mestril and Aton, 2017). Arc mRNA and Arc protein expression are induced in specific brain circuits in vivo by increased neuronal activity (Miyashita et al, J Neurosci 2009) or by prior learning (Carter, Mifsud, & Reul, 2015; Czerniawski et al, 2011; Fellini and Morellini, 2013; Guzowski, Setlow, Wagner, & McGaugh, 2001). The level of expression of Arc mRNA in the hippocampus immediately following training on a hippocampus-dependent task is a predictor of subsequent memory performance (Guzowski et al, 2001)

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