Elucidating the role of nucleus accumbens activity in the propensity to attribute incentive salience to reward cues

阐明伏隔核活动在将激励显着性归因于奖励线索的倾向中的作用

基本信息

批准号：
10319521
负责人：
Cristina Emma Maria-Rios
金额：
$ 4万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-01 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10319521
关键词：
Academia Addictive Behavior Animal Model Attention Automobile Driving Award Behavior Behavioral Biological Markers Cell Nucleus Cells Complex Cues Development Drug usage Electrophysiology (science)Environment Exhibits Faculty Food Glutamates Goals Hippocampus (Brain)Hyperactivity Impulsivity Incentives Individual Individual Differences Lead Learning Lesion Link Manuscripts Mediating Medical Modeling Motivation Neural Pathways Neurobiology Neurons Nucleus Accumbens Outcome Partner in relationship Patients Pattern Phase Phenotype Play Positioning Attribute Predictive Value Predisposing Factor Predisposition Prevention strategy Process Property Psychopathology Publications Rattus Recording of previous events Relapse Research Rewards Risk Risk Factors Role Signal Transduction Site Synapses Synaptic Transmission Technical Expertise Testing Therapeutic Training Translating Vulnerable Populations Work addiction career classical conditioning designer receptors exclusively activated by designer drugs drug of abuse drug relapse early life adversity early life stress effective therapy endophenotype experimental study high risk in vivo incentive salience individual variation interest model building neural circuit neurobiological mechanism neuromechanism neuronal circuitry neuropsychiatric disorder optogenetics patch clamp psychiatric symptom resilience response sample fixation tenure track trait transmission process vector

项目摘要

ABSTRACT Cue-reward associations are critical for developing adaptive responses to cues that signal the availability of food, mating opportunities, and other rewards. During associative learning, cues acquire predictive value, meaning they become linked to an explicit representation of the outcome, but in some instances, they may also acquire incentive salience, meaning they take on some of the attractive and motivational properties of the reward. The excessive attribution of incentive or motivational value can result in cues gaining excessive control over behavior, and lead to maladaptive responses such as those associated with addiction. But the propensity to attribute cues with incentive salience is highly variable and seems to greatly depend on the way individuals learn cue-reward associations. Using the “sign- and goal-tracking” rat model of associative learning we can specifically study individual variation in the propensity to attribute incentive salience to reward cues, and dissect the neurobiological mechanism underlying predisposition to cue-driven psychopathologies like addiction. Compared to “goal-trackers” (GTs), “sign-trackers” (STs) not only use reward cues as predictors, but also attribute them with incentive salience and find them rewarding, resulting in increased motivation towards and fixation on these cues. STs are more impulsive as well as susceptible to cue-induced reinstatement or “relapse” of drugs of abuse when compared to GTs, making this an excellent model to study predisposition to addiction-like behaviors. The focus of this proposal is on the nucleus accumbens (NAc), a region known to be a critical component of the “motive circuit”. STs and GTs exhibit different cue- and reward-evoked patterns of activity in the NAc during Pavlovian learning, but it remains to be determined what neurobiological mechanisms give rise to these different NAc activity profiles and how they may account for the ST/GT phenotype. The proposed experiments will test the hypothesis that there are functional differences between STs and GTs in the strength of synaptic inputs to the NAc, particularly from regions like the ventral hippocampus (vHPC), which is known to be necessary for the attribution of incentive salience. Determining the specific neuronal properties and neural pathways involved in the attribution of incentive salience will increase our understanding on the specific risk factors associated with addiction vulnerability and lead to better biomarkers and tailored therapeutic approaches to treat individuals at higher risk of addiction.

抽象的提示-奖励关联对于开发对信号的适应性反应至关重要，这些提示表明食物的可用性，在联想学习过程中，线索获得了预测价值和意义。它们与结果的明确表示联系在一起，但在某些情况下，它们也可能获得激励显着性，意味着它们具有奖励的一些吸引力和激励特性。过度归因激励或动机价值可能导致线索获得对行为的过度控制，并导致适应不良反应，例如与成瘾相关的反应，但归因于线索的倾向。激励显着性变化很大，似乎很大程度上取决于个人学习提示奖励的方式使用联想学习的“符号和目标跟踪”大鼠模型，我们可以专门研究。将激励显着性归因于奖励线索的倾向的个体差异，并剖析比较了成瘾等线索驱动的精神病理学倾向的神经生物学机制。与“目标追踪者”（GT）相比，“信号追踪者”（ST）不仅使用奖励线索作为预测因子，而且还将它们归因于具有激励显着性，并发现它们是有益的，从而增加对这些的动力和关注 ST 更容易冲动，并且更容易受到提示诱导的滥用药物的恢复或“复发”的影响。与 GT 相比，这使其成为研究成瘾行为倾向的绝佳模型。该提案的重点是伏隔核（NAc），该区域被认为是大脑的关键组成部分 ST 和 GT 在 NAc 中表现出不同的提示和奖励诱发活动模式。巴甫洛夫学习，但仍有待确定是什么神经生物学机制引起了这些不同的 NAc 活性概况以及它们如何解释 ST/GT 表型拟议的实验将进行测试。假设 ST 和 GT 之间在突触输入强度方面存在功能差异 NAc，特别是来自腹侧海马 (vHPC) 等区域，已知该区域对于确定激励显着性的特定神经特性和神经通路。激励显着性的归因将增加我们对与相关的特定风险因素的理解成瘾脆弱性并导致更好的生物标志物和定制的治疗方法来治疗个体成瘾的风险更高。