The Sleep-Wake Cycle in the Nicotinic Alpha-9 Acetylcholine Receptor Subunit Knock-Out Mice.

Natalia Madrid-López,Paul H Délano,Alejandro Bassi,Jorge Estrada,Javier Díaz,Adrián Ocampo-Garcés

doi:10.3389/fncel.2017.00302

Natalia Madrid-López, Paul H Délano + Show 4 more

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https://doi.org/10.3389/fncel.2017.00302

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Abstract

There is a neural matrix controlling the sleep–wake cycle (SWC) embedded within high ranking integrative mechanisms in the central nervous system. Nicotinic alpha-9 acetylcholine receptor subunit (alpha-9 nAChR) participate in physiological processes occurring in sensory, endocrine and immune systems. There is a relationship between the SWC architecture, body homeostasis and sensory afferents so that disruption of afferent signaling is expected to affect the temporal organization of sleep and wake states. The analysis of the SWC of 9 nAChR knock-out animals may help to reveal the contribution of alpha-9 nAChR to sleep chronobiological determinants. Here we explore the polysomnogram in chronically implanted alpha-9 nAChR knock-out (KO) and wild-type (WT) individuals of the hybrid CBA/Sv129 mouse strain. Records were obtained in isolation chambers under a stable 12:12 light:dark cycle (LD). To unmask the 24-h modulation of the SWC a skeleton photoperiod (SP) protocol was performed. Under LD the daily quota (in %) of wakefulness (W), NREM sleep and REM sleep obtained in KO and WT animals were 45, 48 and 7, and 46, 46 and 8 respectively. Both groups exhibit nocturnal phase preference of W as well as diurnal and unimodal phase preference of NREM and REM sleep. The acrophase mean angles of KO vs. WT genotypes were not different (Zeitgeber Time: 6.5 vs. 14.9 for W, 4.3 vs. 2.8 for NREM sleep and 5.3 vs. 3.4 for REM sleep, respectively). Transference to SP do not affect daily state quotas, phase preferences and acrophases among genotypes. Unmasking phenomena of the SWC such as wake increment during the rest phase under SP was evident only among WT mice suggesting the involvement of retinal structures containing alpha-9 nAChR in masking processes. Furthermore, KO animals exhibit longer NREM and REM sleep episodes that is independent of illumination conditions. Consolidated diurnal NREM sleep contributed to obtain higher values of NREM sleep delta-EEG activity among KO mice during rest phase. In conclusion, circadian and sleep homeostatic aspects of the SWC are operative among alpha-9 nAChR KO animals. We propose that alpha-9 nAChR participate in retinal signaling processes responsible of the positive masking of sleep by light.

Highlights

The temporal organization of the sleep–wake cycle (SWC) of mammals exhibit specie-specific characteristics
NREM sleep and REM sleep do not differ between alpha9-nAchR KO individuals and their WT littermates [mixed ANOVA, factor “genotype”: F(1,14) = 2.26, p = 0.129; F(1,14) = 3.39, p = 0.0870; and F(1,14) = 0.52, p = 0.481, for W, NREM sleep and REM sleep respectively]
To further analyze the dynamics of NREM sleep EEG delta power density, we explored the build-up of NREM sleep delta activity within consolidated (>2 min) NREM sleep episodes under light:dark cycle (LD) and skeleton photoperiod (SP) during rest and active phases (Figure 6B)

Summary

Introduction

The temporal organization of the sleep–wake cycle (SWC) of mammals exhibit specie-specific characteristics. Mice and most murids including rats and hamsters exhibit nocturnal phase preference of activity determined by circadian processes, where wakefulness is concentrated during the dark phase and sleep states during the light phase (Vivaldi et al, 1994; Yasenkov and Deboer, 2012). Mammals exhibit relatively stable amount of sleep states cumulated during the 24-h period, a property of SWC physiology that evidences sleep homeostatic mechanisms that preserve daily sleep and wake quotas (Dijk, 2009). Together with the circadian effect of the light-dark cycle that determines the quotidian phase adjustment enabling the photic entrainment of the circadian system, retinal illumination exerts direct effect on sleep– wake state generators, in a phenomenon known as photic masking (Hubbard et al, 2013). The direct effect of the visual system on sleep state generators has been supposed to rely on non-image forming proyections of a subpopulation of retinal ganglion cells termed intrinsically photosensitive (ipRGCs, Pickard and Sollars, 2011)

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