Regulation of Nucleus Accumbens Neurons by Sleep Deprivation

摘要 睡眠对情绪和动机状态有很大影响。睡眠障碍是几乎所有疾病的共同发病。 情绪和动机障碍，包括药物成瘾、抑郁和精神分裂症。的确，睡觉 干扰不仅是一种症状后果，而且也是这些疾病进展的原因。 病态的情绪状态。临床统计显示，失眠症患者更容易吸毒 上瘾。尽管有如此明显的重要性，但人们对睡眠障碍如何调节睡眠时间知之甚少。 控制情绪和动机的大脑关键区域的功能。这个应用程序关注的是这个重要但 开发不足的研究领域。这项拟议的研究试图描述睡眠剥夺(SD) 调节兴奋性和抑制性突触以及脑内神经元的膜特性 伏隔核(NAC)，一个控制情绪和动机输出的大脑区域。NAC出现故障 会导致几种病态的情绪和激励状态，如吸毒成瘾、焦虑和 抑郁症。尽管临床统计数据显示，睡眠障碍的强度与 这些情绪障碍的程度，还有待确定NAC神经元在睡眠中是如何改变的- 受惊扰的受试者。通过观察SD对突触传递和膜特性的影响，探讨SD对突触传递的影响。 NAC神经元，这项拟议的工作将提供一个相对全面的关于睡眠障碍如何 影响NAC的功能输出。指导这项拟议研究的中心假设是SD 差异性调节NAC的兴奋性和抑制性突触活动以及膜兴奋性 神经元，导致NAC神经元功能输出失真。这一假设将通过追查来检验 三个特定的目标：1)表征SD诱导的NAC神经元的突触适应；2)表征SD- 3)探讨SD对NAC神经元膜适应性的影响。 激励行为。拟议的工作与国家卫生研究院的任务密切相关，因为预期结果 将提供对睡眠和睡眠障碍如何调节大脑关键区域的基本理解，即 卷入了大量的情绪和动机障碍。

Abstract Sleep profoundly affects emotional and motivational states. Sleep disturbance is a co-morbidity in almost all emotional and motivational disorders including drug addiction, depression, and schizophrenia. Indeed, sleep disturbance is not only a symptomatic consequence, but also a causal factor for the progression of these pathological emotional states. Clinical statistics show that people with insomnia are more prone to drug addiction. Despite such apparent significance, little is known about how sleep disturbance regulates the function of key brain regions that control emotion and motivation. This application focuses on this important yet under-explored research area. The proposed research attempts to characterize how sleep deprivation (SD) regulates both excitatory and inhibitory synapses as well as the membrane properties of neurons within the nucleus accumbens (NAc), a brain region that gates emotional and motivational output. Malfunction of the NAc contributes to several pathological emotional and motivational states, such as drug addiction, anxiety, and depression. Although clinical statistics shows a clear correlation between the intensity of sleep disturbance and the degree of these emotional disorders, it remains to be determined how NAc neurons are altered in sleep- disturbed subjects. By characterizing the effect of SD on synaptic transmission and membrane properties of NAc neurons, the proposed work will provide a relatively comprehensive picture about how sleep disturbance affects the functional output of the NAc. The central hypothesis guiding the proposed research is that SD differentially regulates excitatory and inhibitory synaptic activities as well as the membrane excitability of NAc neurons, resulting in distorted functional output of NAc neurons. This hypothesis will be tested by pursuing three specific aims: 1) characterize SD-induced synaptic adaptations in NAc neurons; 2) characterize SD- induced membrane adaptations in NAc neurons; and 3) explore the impact of SD on NAc-based emotional and motivational behaviors. The proposed work is closely relevant to NIH's mission in that the expected outcome will provide essential understanding about how sleep and sleep disturbance regulate a key brain region that is involved in a large number of emotional and motivational disorders.