Individual differences in sleep-related neural dynamics in sign trackers vs goal trackers

项目摘要/摘要 在人类中，睡眠改变与酒精和药物滥用障碍的风险增加有关 有些人是精挑细选的。这是一个鸡和蛋的问题，在临床上往往很难回答。 人群：这些人的睡眠差异是否代表了一种潜在的睡眠结构 促进上瘾的行为，或者睡眠障碍是由药物或酒精的消费引起的？ 在这里，我们使用并扩展了一个临床前模型来理解睡眠剥夺和 追求报酬的行为。由以下因素触发的激励状态存在个体差异 与奖励相关的暗示，一些人经历了更强烈的欲望和渴望(即激励 突出)当接触到提示时比其他人更明显。这些个体差异可以在啮齿动物身上使用 巴甫洛夫条件化方法(PCA)，其中离散的和可定位的线索与食物配对 奖励。当线索可用时，一些老鼠会走近它并与之互动(“符号追踪器”，STS)； 其他老鼠将接近送餐地点(“目标追踪器”，GTS)。STS与GTS的区别 代表稳定的行为特征，在很大程度上是由基因决定的，并与 其他心理特征(如冲动)和神经生物学特征(如多巴胺能活动改变)。 我们的中心假设是，睡眠剥夺在不同的学习阶段对奖赏相关的学习有不同的影响 个人。在目标1中，我们将通过剥夺大量男性和 并询问受扰睡眠如何改变它们在PCA任务中的奖赏寻求行为。我们的 初步数据显示，睡眠不足会导致手势跟踪行为显著增加 明显失去了更细微的、中间的行为。在目标2中，我们将执行大规模任务--以及 同时来自多个奖赏相关脑区的睡眠相关电生理记录， 包括伏隔核、腹侧苍白球、内侧前额叶皮质和海马体。其中许多 这些区域与动机控制和睡眠调节有关，这使它们成为理想的揭示对象 相关个体在激励突显和睡眠相关动力方面的差异。这件事的意义 该项目有两个方面：我们将建立第一个将睡眠剥夺与个体联系起来的临床前模型 在学习和寻求奖励方面的差异；第二，通过识别不同的 具有不同奖赏寻求表型的个体，这项工作可以转化为使用睡眠脑电来 识别和帮助有吸毒行为或复发倾向的个人。

PROJECT SUMMARY / ABSTRACT In humans, altered sleep is associated with an increased risk of alcohol and substance abuse disorders in some select individuals. This presents a chicken and the egg problem that is often difficult to answer in clinical populations: do the sleep differences in these individuals represent an underlying sleep architecture that promotes addictive behavior, or are the sleep disturbances caused by the consumption of drugs or alcohol? Here, we use and extend a preclinical model to understand the relationship between sleep deprivation and reward-seeking behaviors. There are individual differences in the motivational states that are triggered by reward-related cues, with some individuals experiencing stronger feelings of desire and craving (i.e. incentive salience) when exposed to a cue than others. These individual differences can be modeled in rodents using a Pavlovian Conditioned Approach (PCA) procedure, in which a discrete and localizable cue is paired with food reward. When the cue is available, some rats will approach and interact with it (“sign trackers”, STs); whereas other rats will approach the site of food delivery (“goal trackers”, GTs). The differences between STs and GTs represent stable behavioral traits that are largely genetically determined, and are associated with differences in other psychological (e.g. impulsivity) and neurobiological (e.g. altered dopaminergic activity) features. Our central hypothesis is that sleep deprivation differentially impacts reward-related learning in different individuals. In Aim 1, we will causally test this hypothesis by sleep-depriving a very large number of male and female rodents and asking how the disturbed sleep alters their reward-seeking behaviors in the PCA task. Our preliminary data show that sleep deprivation causes a remarkably robust increase in sign-tracking behavior with a clear loss of more nuanced, intermediate behaviors. In Aim 2, we will carry out massive-scale task- and sleep-related electrophysiological recordings simultaneously from multiple reward-related brain regions, including the nucleus accumbens, ventral pallidum, medial prefrontal cortex and hippocampus. Many of these areas are implicated in both motivational control and sleep regulation, making them ideal candidates to reveal correlated individual differences in incentive salience and sleep-related dynamics. The significance of this project is two-fold: we will establish the first preclinical model that relates sleep deprivation to individual differences in learning and reward-seeking; and secondly, by identifying neural signatures that differ across individuals with distinct reward-seeking phenotypes, this work can be translated into using sleep EEG to identify and help individuals who are prone to drug-seeking behavior or relapse.