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

项目概要/摘要 个人使用复杂的流程来做出选择和确定行动的优先级， 奖励和相关的刺激基于先前的经验。在现代环境中，我们 周围有大量的刺激物，这些刺激物争夺我们的注意力，常常阻碍目标导向的 行为刺激，或我们环境中的线索，通过巴甫洛夫学习获得对行为的控制，例如 先前预测奖励的中性刺激获得了动机属性， 转化为有吸引力和令人满意的激励刺激。刺激是否仅仅作为一个预测因素 奖励，或也作为一种激励刺激，个体之间的差异。在不同物种中， 个体在奖励线索偏向选择和控制行为的程度上各不相同。神经 然而，这种个体差异的基础过程仍有待确定。拟议 研究中，我们将利用大鼠线索动机行为的自然变化，并采用新的工具， 识别潜在神经回路的关键组件。当老鼠接触到巴甫洛夫 有条件的方法范式，一些，被称为“目标追踪者”，主要是属性的预测价值， 离散的食物相关的线索;而其他人，称为“标志追踪者”也将激励显着性归因于 提示因此，这种动物模型使我们能够分离促进神经元功能的神经过程。 预测与激励学习以及由此产生的行为。使用该模型， 丘脑核（PVT）已经成为一个关键节点，它起着整合自上而下输入的作用 皮层控制中心和自下而上的皮层下唤醒中心，反过来，引导线索动机 行为具体来说，PI实验室最近的研究表明， 当对PVT的皮层下输入比皮层输入更重时表现出来。因此，在本发明中， 刺激皮层输入到PVT减弱了信号跟踪行为，这可能发生 将控制权从自下而上转移到自上而下。PVT中的神经代码 反映了综合输入和结果的目标导向或适应不良的行为仍然是 这一点已经确定，并将成为当前提案的重点。基于放射性的钙成像将 结合基于机器学习的“深度表型分析”来确定神经特征 预测随后的线索动机行为和个体差异的PVT。在 此外，从前边缘皮层到PVT的“自上而下”输入将使用化学遗传学刺激 并且将评估PVT和脑-行为关系中的所得神经元活动。这些 研究将产生一个管道，未来的研究将依赖于更深入地探测神经回路 环境中的刺激通过这种方式来控制和刺激行为。

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.