Brain Circuit Mechanisms for Reward Cue Attraction

毒瘾是指追求和消费毒品的过度动机。部分 这一动机被认为涉及将价值归因于与药物配对的线索。提示： 奖励，包括药物和食物，可以成为激励目标，吸引人们的注意和 行为。在大脑中，负责这一过程的区域的基本轮廓是已知的，并且 包括伏核(NAC)和腹侧苍白球(VP)。尽管这些地区是 作为一个双向连接的电路，人们对动力是如何产生的知之甚少 电路动力学。为了解决这一问题，拟议的研究将纳入一种名为 化学遗传学用于相对非侵入性的“远程控制”大脑活动的扰动。 将这种方法与转基因传递策略相结合，我们将既增加又减少 连接NAC和VP的通路中的活动，以评估它们在动机中的作用 对奖励线索的吸引力。 这一激励过程的例子是手势跟踪行为，在这种行为中，动物 贪婪地参与到预测奖励的线索中来。在拟议的研究中，Connections NAC和VP之间的关系将使用DREADD进行操作，以评估这些 获得和表达手势跟踪行为的途径。神经活动的记录 基因表达分析将补充这些实验，以建立神经 随着动机行为的改变而改变的激活模式。我们也将同样地 测试神经元在表达乙酰胆碱的VP中的作用，这些神经元接受NAC输入，并 假设是为了将注意力引导到奖励线索上。结果显示NA-VP电路如何 控制动机，以及神经活动特征映射到增加和减少 动机，将提供关键的参考点，以了解如何途径特异性 大脑活动的变化可能会导致上瘾行为中的过度动机。这个 该程序的相对非侵入性也具有破坏的翻译潜力 对药物相关刺激的严重过度反应。

Drug addiction involves an excessive motivation to pursue and consume drugs. Part of this motivation is thought to involve the attribution of value to drug-paired cues. Cues for rewards, including drugs and food, can become motivational targets and attract attention and behavior. In the brain, a basic sketch of areas responsible for this process is known and includes the nucleus accumbens (NAc) and ventral pallidum (VP). Although these areas are bidirectionally connected as a circuit, little is known about how motivation arises out of their circuit dynamics. To address this, the proposed research will incorporate a method called chemogenetics for relatively non-invasive “remote control” perturbation of brain activity. Combining this method with transgenic delivery strategies, we will both increase and decrease activity in pathways connecting the NAc and VP to evaluate their role in the motivational attraction to reward cues. This motivational process is exemplified by sign-tracking behavior, in which animals appetitively engage with a cue predicting reward. In the proposed research, connections between the NAc and VP will be manipulated using DREADDs to assess the role of these pathways in acquiring and expressing the sign-tracking behavior. Recordings of neural activity and gene expression assays will complement these experiments in order to establish neural activation patterns that change in register with changes in motivated behavior. We will similarly test the role of neurons in the VP expressing acetylcholine, which receive NAc input and are hypothesized to guide attention towards reward cues. Results showing how NA-VP circuits control motivation, and what neural activity signatures map on to increases and decreases in motivation, will provide critical reference points for an understanding of how pathway-specific changes in brain activity could contribute to excessive motivation in addictive behaviors. The relative non-invasiveness of the procedure also carries translational potential for disrupting severely excessive reactions to drug-associated stimuli.