Brain Circuit Mechanisms for Reward Cue Attraction

药物成瘾涉及追求和消费药物的过度动机。的一部分 这种动机被认为涉及将价值归因于药物配对线索。的线索 奖励，包括药物和食物，可以成为激励目标，吸引注意力， 行为在大脑中，负责这一过程的区域的基本草图是已知的， 包括腹侧苍白球（VP）和脑桥核（NAc）。虽然这些地区是 作为一个双向连接的电路，很少有人知道动机是如何产生的， 电路动力学为了解决这个问题，拟议的研究将采用一种称为 化学遗传学用于相对非侵入性的“远程控制”脑活动扰动。 将这种方法与转基因递送策略相结合， 在连接NAc和VP的途径中的活动，以评估它们在激励中的作用 奖励线索的吸引力 这种动机过程的例子是符号追踪行为，其中动物 食欲与预测奖励的线索联系在一起。在拟议的研究中， NAc和VP之间的关系将使用DREADD进行操纵，以评估这些 获取和表达符号追踪行为的途径。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 激活模式随着动机行为的变化而变化。我们同时也会 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， 引导注意力转向奖励线索。结果显示NA-VP电路 控制动机，以及神经活动签名映射到增加和减少， 动机，将提供关键的参考点，了解如何路径特定 大脑活动的变化可能导致成瘾行为的过度动机。的 该过程的相对非侵入性也具有破坏 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.