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

信号追踪器与目标追踪器中睡眠相关神经动力学的个体差异

• 批准号: 10220524
• 负责人: Omar Jamil Ahmed
• 金额: $ 39万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10220524
• 关键词: Acute; Addictive Behavior; Affect; Alcohol abuse; Alcohol consumption; Alcohols; Area; Attention; Behavior; Behavioral; Brain region; Clinical; Consumption; Corpus striatum structure; Cues; Data; Data Set; Disease; Dopamine; Electroencephalography; Electrophysiology (science); Environment; Exposure to; Feeling; Female; Food; Future; Globus Pallidus; Goals; Hippocampus (Brain); Human; Impulsivity; Individual; Individual Differences; Intervention; Lead; Learning; Link; Medial; Methods; Modeling; Motivation; Neurobiology; Neurons; Nucleus Accumbens; Performance; Pharmaceutical Preparations; Phenotype; Population; Population Control; Pre-Clinical Model; Precision Health; Prefrontal Cortex; Procedures; Rattus; Regulation; Relapse; Rewards; Risk; Risk Factors; Rodent; Rodent Model; Role; Site; Sleep; Sleep Architecture; Sleep Deprivation; Sleep disturbances; Stimulus; Substance Use Disorder; Substance abuse problem; System; Testing; Translating; Work; addiction; alcohol risk; attentional control; base; chicken egg; cholinergic; cohort; craving; drug craving; drug seeking behavior; experience; experimental study; improved; incentive salience; individual variation; innovation; insight; interest; learned behavior; male; motivated behavior; neural circuit; neuroregulation; novel; pre-clinical; psychologic; receptor; relating to nervous system; response; sleep regulation; trait

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.

项目总结/摘要 在人类中，睡眠改变与酒精和物质滥用障碍的风险增加有关， 有些人选择的人。这就提出了一个鸡和蛋的问题，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， 促进成瘾行为，或者睡眠障碍是由药物或酒精的消耗引起的？ 在这里，我们使用并扩展了一个临床前模型，以了解睡眠剥夺与睡眠不足之间的关系。 寻求奖励的行为。个体的动机状态存在差异， 与奖励相关的线索，一些人会经历更强烈的欲望和渴望（即激励） 当你接触到一个线索时，比其他人更明显。这些个体差异可以在啮齿动物中使用 巴甫洛夫条件方法（PCA）程序，其中一个离散的和可定位的线索与食物配对 奖励当提示可用时，一些大鼠会接近并与之互动（“符号追踪者”，ST）; 其它大鼠将接近食物递送的位置（“目标跟踪器”，GT）。ST和GT的区别 代表了稳定的行为特征，这些特征在很大程度上是由基因决定的，并且与以下方面的差异有关： 其他心理学（如冲动）和神经生物学（如多巴胺能活性改变）特征。 我们的中心假设是，睡眠剥夺对不同年龄组的奖励相关学习产生不同的影响。 个体在目标1中，我们将通过剥夺大量男性和女性的睡眠， 雌性啮齿动物，并询问睡眠紊乱如何改变它们在PCA任务中的奖励寻求行为。我们 初步数据显示，睡眠不足会导致跟踪信号行为的显著增加， 明显失去了更微妙的中间行为。在目标2中，我们将执行大规模任务， 睡眠相关的电生理记录同时从多个奖励相关的大脑区域， 包括伏隔核、腹侧苍白球、内侧前额叶皮质和海马体。许多这些 这些区域与动机控制和睡眠调节有关，使它们成为揭示 相关的个体差异的激励显着性和睡眠相关的动态。其意义 该项目是双重的：我们将建立第一个临床前模型，将睡眠剥夺与个人 学习和奖励寻求的差异;其次，通过识别不同的神经信号， 具有不同的奖励寻求表型的个体，这项工作可以转化为使用睡眠EEG， 识别并帮助有吸毒倾向或复吸倾向的人。