Capturing the neural signature of the paraventricular thalamus that underlies individual variability in cue-motivated behavior

项目摘要/摘要 个人使用复杂的流程做出选择并确定行动的优先顺序，这些流程将价值分配给 基于先前经验的奖励和相关刺激。在我们的现代环境中，我们是 被大量的刺激所包围，这些刺激争夺我们的注意力，并经常阻碍目标导向 行为。我们环境中的刺激或暗示通过巴甫洛夫式的学习来获得对行为的控制，例如 先前预测奖励中性刺激获得了激励属性并因此 转化为有吸引力和令人向往的激励刺激。一种刺激是否只起到预测作用 奖励的多少，或者也可以作为一种激励刺激，因人而异。跨物种， 个体在奖励线索、偏向选择和控制行为的程度上存在差异。神经学 然而，这种个体差异背后的过程仍有待确定。在建议的 研究我们将利用大鼠线索动机行为的自然变异，并使用新的工具来 确定潜在神经回路的关键组件。当老鼠暴露在巴甫洛夫病毒中时 有条件的方法范式，一些被称为“目标跟踪器”，主要将预测值归因于 与食物相关的离散提示；而其他被称为“符号追踪器”的人也将激励突显归因于 这就是暗示。因此，这个动物模型允许我们分离促进 预测性学习与激励性学习以及由此产生的行为。使用这种模式，室旁 丘脑核团(PVT)已成为整合自上而下信息输入的关键节点 皮质控制中心和自下而上的皮质下唤醒中心，进而引导线索激发 行为。具体地说，PI实验室最近的研究表明，手势跟踪行为 当PVT的皮质下输入比皮质输入更重时表现出来。因此， 刺激皮质对PVT的输入减弱了手势跟踪行为，这可能会发生 通过将控制从自下而上转移到自上而下。PVT内的神经编码 反映了综合输入和目标导向或适应不良行为的结果仍有待于 已经确定，并将成为当前提案的重点。基于荧光的钙成像将是 与基于机器学习的“深度表型”相结合来确定神经特征 预测随后的线索动机行为的PVT，是个体差异的基础。在……里面 此外，从大脑皮层到室旁核的“自上而下”的输入将被化学遗传学刺激。 并将评估由此产生的PVT中的神经元活动和脑-行为关系。这些 研究将产生一条管道，未来的研究将依赖于更深入地探测神经回路 通过这种方式，环境中的刺激可以控制和刺激行为。

PROJECT SUMMARY/ABSTRACT Individuals make choices and prioritize actions using complex processes that assign value to rewards and associated stimuli based on prior experience. In our modern environment, we are surrounded by an abundance of stimuli that fight for our attention and often hinder goal-directed behavior. Stimuli, or cues in our environment, attain control over behavior via Pavlovian learning, such that previously neutral stimuli that predict reward acquire motivational properties and are thereby transformed into attractive and desirable incentive stimuli. Whether a stimulus acts solely as a predictor of reward, or also serves as an incentive stimulus, differs between individuals. Across species, individuals vary in the degree to which reward cues bias choice and control behavior. The neural processes that underlie this individual variation, however, remain to be determined. In the proposed studies we will exploit natural variation in cue-motivated behavior in rats and employ novel tools to identify critical components of the underlying neural circuitry. When rats are exposed to a Pavlovian conditioned approach paradigm, some, termed “goal-trackers”, primarily attribute predictive value to a discrete food-associated cue; whereas others, termed “sign-trackers” also attribute incentive salience to the cue. This animal model, therefore, allows us to dissociate the neural processes that promote predictive vs. incentive learning and the resultant behaviors. Using this model, the paraventricular nucleus of the thalamus (PVT) has emerged as a key node that acts to integrate input from top-down cortical control centers and bottom-up subcortical arousal centers and, in turn, guide cue-motivated behavior. Specifically, recent research from the PI’s laboratory suggests that sign-tracking behavior manifests when subcortical input to the PVT is weighed more heavily than cortical input. Thus, stimulation of cortical input to the PVT attenuates sign-tracking behavior, and this presumably occurs by shifting the control from bottom-up to top-down processes. The neural code within the PVT that reflects the integrated input and results in goal-directed or maladaptive behaviors remains to be determined and will be the focus of the current proposal. Fluorescence-based calcium imaging will be used in conjunction with machine-learning based “deep phenotyping” to determine the neural signature of the PVT that predicts subsequent cue-motivated behavior and underlies individual variation. In addition, “top-down” input from the prelimbic cortex to the PVT will be stimulated using chemogenetics and the resultant neuronal activity in the PVT and brain-behavior relationship will be assessed. These studies will generate a pipeline that future studies will rely on to more deeply probe the neural circuits by which stimuli in the environment attain control over, and incite, behavior.