Regulation of Nucleus Accumbens Neurons by Sleep Deprivation

摘要 睡眠深刻地影响情绪和动机状态。睡眠障碍是一种并发症，在几乎所有 情绪和动机障碍，包括药物成瘾、抑郁症和精神分裂症。真的，睡吧 干扰不仅是一个症状的后果，但也是一个因果因素的进展，这些 病态的情绪状态临床统计显示，失眠的人更容易吸毒 成瘾尽管如此明显的意义，很少有人知道睡眠障碍如何调节 控制情绪和动机的关键大脑区域的功能。这个应用程序的重点是这个重要的，但 探索不足的研究领域。这项拟议中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神经元内的膜特性。 神经核（NAc），一个控制情绪和动机输出的大脑区域。NAc的故障 有助于几种病理性的情绪和动机状态，如吸毒成瘾，焦虑， 萧条尽管临床统计显示睡眠障碍的强度与睡眠质量之间存在明显的相关性， 这些情绪障碍的程度，还有待确定NAc神经元如何在睡眠中改变- 不安的主题。通过表征SD对突触传递和细胞膜特性的影响， NAc神经元，拟议的工作将提供一个关于睡眠障碍如何相对全面的图片 影响NAc的功能输出。指导拟议研究的中心假设是，SD 差异调节兴奋性和抑制性突触活动以及NAc的膜兴奋性 神经元，导致NAc神经元的扭曲功能输出。这一假设将通过追踪 三个具体目标：1）表征SD诱导的NAc神经元突触适应; 2）表征SD- 在NAc神经元中诱导膜适应;和3）探索SD对基于NAc的情绪和 动机行为拟议的工作与NIH的使命密切相关，因为预期的结果 将提供关于睡眠和睡眠障碍如何调节关键大脑区域的基本理解， 涉及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.