Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK.
Department of Experimental Psychology, University of Oxford, South Parks Road, Oxford, OX1 3UD, UK.
Transl Psychiatry. 2018 Aug 14;8(1):154. doi: 10.1038/s41398-018-0199-2.
Sleep EEG spindles have been implicated in attention, sensory processing, synaptic plasticity and memory consolidation. In humans, deficits in sleep spindles have been reported in a wide range of neurological and psychiatric disorders, including schizophrenia. Genome-wide association studies have suggested a link between schizophrenia and genes associated with synaptic plasticity, including the Gria1 gene which codes for the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. Gria1 mice exhibit a phenotype relevant for neuropsychiatric disorders, including reduced synaptic plasticity and, at the behavioural level, attentional deficits leading to aberrant salience. In this study we report a striking reduction of EEG power density including the spindle-frequency range (10-15 Hz) during sleep in Gria1 mice. The reduction of spindle-activity in Gria1 mice was accompanied by longer REM sleep episodes, increased EEG slow-wave activity in the occipital derivation during baseline sleep, and a reduced rate of decline of EEG slow wave activity (0.5-4 Hz) during NREM sleep after sleep deprivation. These data provide a novel link between glutamatergic dysfunction and sleep abnormalities in a schizophrenia-relevant mouse model.
睡眠脑电纺锤波被认为与注意力、感觉处理、突触可塑性和记忆巩固有关。在人类中，睡眠纺锤波的缺陷已在广泛的神经和精神疾病中被报道，包括精神分裂症。全基因组关联研究表明，精神分裂症与与突触可塑性相关的基因之间存在关联，包括编码α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体 GluA1 亚基的 Gria1 基因。Gria1 小鼠表现出与神经精神疾病相关的表型，包括突触可塑性降低，以及在行为水平上注意力缺陷导致异常的突显。在这项研究中，我们报告了 Gria1 小鼠在睡眠期间 EEG 功率密度（包括纺锤波频率范围 10-15 Hz）显著降低。Gria1 小鼠的纺锤波活动减少伴随着 REM 睡眠片段的延长，在基线睡眠期间枕叶导线上的 EEG 慢波活动增加，以及睡眠剥夺后 NREM 睡眠期间 EEG 慢波活动（0.5-4 Hz）下降速度减慢。这些数据为精神分裂症相关小鼠模型中谷氨酸能功能障碍与睡眠异常之间提供了新的联系。
