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

摘要 线索-奖励关联对于发展对暗示食物可获得性的适应性反应至关重要， 交配机会和其他奖励在联想学习过程中，线索获得预测值， 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 激励显著性，这意味着他们采取了一些有吸引力和激励性质的奖励。的 对激励或动机价值的过度归因会导致线索对行为的过度控制， 并导致适应不良的反应，如与成瘾有关的反应。但把线索归因于 激励显著性是高度可变的，似乎在很大程度上取决于个人学习线索奖励的方式 协会.使用"符号和目标跟踪"大鼠模型的联想学习，我们可以具体研究 个人差异的倾向，属性激励显着性奖励线索，并剖析了 神经生物学机制潜在的倾向线索驱动的精神病理学，如成瘾。相比 对于"目标追踪者"（GT），"符号追踪者"（ST）不仅将奖励线索作为预测因素， 具有激励显著性，并发现它们是有益的，从而增加了对这些的动机和固定 线索性病患者更易冲动，也更容易因线索而复吸或"复发"。 与GT相比，这是一个很好的模型来研究成瘾样行为的倾向。的 这一建议的重点是在核心的核（NAc），一个已知的区域是一个关键组成部分， "动机电路"。ST和GT在NAc中表现出不同的提示和奖励诱发的活动模式， 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活性谱及其如何解释ST/GT表型。拟议的实验将测试 这一假说认为，ST和GT之间在突触输入的强度方面存在功能差异， NAc，特别是来自腹侧海马（vHPC）等区域，这是已知的必要条件。 激励显著性的归因。确定特定的神经元特性和神经通路参与 激励显著性的归因将增加我们对与以下因素相关的特定风险因素的理解： 成瘾的脆弱性，并导致更好的生物标志物和量身定制的治疗方法，以治疗个人在 成瘾的风险更高。

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.