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发出食物可获得性信号的线索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，线索获得预测性价值、意义 它们与结果的显式表示相关联，但在某些情况下，它们还可能获得 激励性突出，意味着他们具有奖励的一些有吸引力和激励性的特性。这个 对激励或激励价值的过度归因会导致线索获得对行为的过度控制， 并导致适应不良反应，如与上瘾有关的反应。但将线索归因于 对于激励性，显著程度是高度可变的，而且似乎在很大程度上取决于个体学习线索-奖励的方式 联想。利用“手势和目标跟踪”的大鼠联想学习模型，我们可以具体研究 将激励显著归因于奖励线索的倾向的个体差异，并剖析了 倾向于线索驱动的精神病态的神经生物学机制，如成瘾。相比较 对于“目标跟踪者”(GTS)来说，“符号跟踪者”(STS)不仅使用奖励线索作为预测因素，而且还将其归于奖励线索 具有激励性的突显，并发现它们是有回报的，从而增加了对这些东西的动机和执着 暗示。STS更容易冲动，也更容易在线索诱导下恢复或“复发”滥用药物 与GTS相比，这使其成为研究类成瘾行为易感性的极佳模型。这个 这项提议的重点是伏隔核(NAC)，这是已知的一个区域，是 “运动回路”。STS和GTS在NAC中表现出不同的线索和奖赏诱发活动模式 巴甫洛夫式学习，但什么神经生物学机制导致这些不同还有待确定 NAC活性谱以及它们如何解释ST/GT表型。拟议中的实验将检验 STS和GTS在突触输入强度上存在功能差异的假设 NAC，特别是来自腹侧海马区(VHPC)的NAC，已知这是 激励显著的归因。确定特定的神经元属性和参与的神经通路 激励显著的归因将增加我们对与以下相关的具体风险因素的理解 并导致更好的生物标记物和量身定做的治疗方法来治疗个人 上瘾的风险更高。

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.