Sleep Phenotyping in a Mouse Model of Extreme Trait Anxiety

Vladimira Jakubcakova,Rainer Landgraf,Mayumi Kimura,Cornelia Flachskamm,David A Slattery

doi:10.1371/journal.pone.0040625

Vladimira Jakubcakova, Rainer Landgraf + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0040625

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Journal: PloS one	Publication Date: Jul 11, 2012
Citations: 27	License type: CC BY 4.0

Affiliation: Max Planck Institute of Psychiatry

Abstract

BackgroundThere is accumulating evidence that anxiety impairs sleep. However, due to high sleep variability in anxiety disorders, it has been difficult to state particular changes in sleep parameters caused by anxiety. Sleep profiling in an animal model with extremely high vs. low levels of trait anxiety might serve to further define sleep patterns associated with this psychopathology.Methodology/Principal FindingsSleep-wake behavior in mouse lines with high (HAB), low (LAB) and normal (NAB) anxiety-related behaviors was monitored for 24 h during baseline and recovery after 6 h sleep deprivation (SD). The amounts of each vigilance state, sleep architecture, and EEG spectral variations were compared between the mouse lines. In comparison to NAB mice, HAB mice slept more and exhibited consistently increased delta power during non-rapid eye movement (NREM) sleep. Their sleep patterns were characterized by heavy fragmentation, reduced maintenance of wakefulness, and frequent intrusions of rapid eye movement (REM) sleep. In contrast, LAB mice showed a robust sleep-wake rhythm with remarkably prolonged sleep latency and a long, persistent period of wakefulness. In addition, the accumulation of delta power after SD was impaired in the LAB line, as compared to HAB mice.Conclusions/SignificanceSleep-wake patterns were significantly different between HAB and LAB mice, indicating that the genetic predisposition to extremes in trait anxiety leaves a biological scar on sleep quality. The enhanced sleep demand observed in HAB mice, with a strong drive toward REM sleep, may resemble a unique phenotype reflecting not only elevated anxiety but also a depression-like attribute.

Highlights

The prevalence of affective disorders increases in a global scale and has negatively contributed to serious health and social problems in recent years [1]
The mouse lines derived from the CD1 strain were inbred for extremes in trait anxiety according to their anxietyrelated behavior on the elevated plus maze (EPM), with HAB mice spending,12%, normal anxietyrelated behavior (NAB) mice spending 30–40%, and LAB mice spending .60% on the open arms of the elevatedplus maze (EPM)
Each line confined the majority of sleep and wakefulness to the light and dark periods, respectively, the amplitude of the light versus dark difference in the amount of each vigilance state was attenuated in HAB relative to NAB and LAB mice (P,0.05, see legend to Figure 1)

Summary

Introduction

The prevalence of affective disorders increases in a global scale and has negatively contributed to serious health and social problems in recent years [1]. The psychopathology of these stress-related mental disorders includes symptoms that reflect disturbances in sleep. Given the considerable overlap of symptoms and causes between anxiety and depression, there is growing interest in finding reliable diagnostic markers in patients. In this respect, the potential of experimental non-human models could be of considerable help to recognize and evaluate the discrete clinical features of various psychopathologies. Sleep profiling in an animal model with extremely high vs. low levels of trait anxiety might serve to further define sleep patterns associated with this psychopathology

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