Thomas Alexia M, Schwartz Michael D, Saxe Michael D, Kilduff Thomas S
Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA 94025, USA.
Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Disease DTA, F. Hoffmann-La Roche Ltd, Switzerland.
Sleep. 2017 Oct 1;40(10). doi: 10.1093/sleep/zsx138.
Neuroligin-3 (NLGN3) is one of the many genes associated with autism spectrum disorder (ASD). Sleep dysfunction is highly prevalent in ASD, but has not been rigorously examined in ASD models. Here, we evaluated sleep/wake physiology and behavioral phenotypes of rats with genetic ablation of Nlgn3.
Male Nlgn3 knockout (KO) and wild-type (WT) rats were assessed using a test battery for ASD-related behaviors and also implanted with telemeters to record the electroencephalogram (EEG), electromyogram, body temperature, and locomotor activity. 24-h EEG recordings were analyzed for sleep/wake states and spectral composition.
Nlgn3 KO rats were hyperactive, exhibited excessive chewing behavior, and had impaired prepulse inhibition to an auditory startle stimulus. KO rats also spent less time in non-rapid eye movement (NREM) sleep, more time in rapid eye movement (REM) sleep, exhibited elevated theta power (4-9 Hz) during wakefulness and REM, and elevated delta power (0.5-4 Hz) during NREM. Beta (12-30 Hz) power and gamma (30-50 Hz) power were suppressed across all vigilance states.
The sleep disruptions in Nlgn3 KO rats are consistent with observations of sleep disturbances in ASD patients. The EEG provides objective measures of brain function to complement rodent behavioral analyses and therefore may be a useful tool to study ASD.
神经连接蛋白3（NLGN3）是众多与自闭症谱系障碍（ASD）相关的基因之一。睡眠功能障碍在ASD中非常普遍，但尚未在ASD模型中进行严格研究。在此，我们评估了Nlgn3基因敲除大鼠的睡眠/觉醒生理和行为表型。
使用一套针对ASD相关行为的测试对雄性Nlgn3基因敲除（KO）大鼠和野生型（WT）大鼠进行评估，并植入遥测器以记录脑电图（EEG）、肌电图、体温和运动活动。对24小时的EEG记录进行睡眠/觉醒状态和频谱成分分析。
Nlgn3基因敲除大鼠活动亢进，表现出过度咀嚼行为，对听觉惊吓刺激的前脉冲抑制受损。基因敲除大鼠在非快速眼动（NREM）睡眠中花费的时间也更少，在快速眼动（REM）睡眠中花费的时间更多，在清醒和快速眼动期间表现出更高的θ波功率（4-9赫兹），在非快速眼动期间表现出更高的δ波功率（0.5-4赫兹）。在所有警觉状态下，β波（12-30赫兹）功率和γ波（30-50赫兹）功率均受到抑制。
Nlgn3基因敲除大鼠的睡眠中断与ASD患者睡眠障碍的观察结果一致。EEG为脑功能提供了客观测量指标，以补充啮齿动物行为分析，因此可能是研究ASD的有用工具。
