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

捕捉室旁丘脑的神经信号，该信号是线索驱动行为个体差异的基础

• 批准号: 10715723
• 负责人: Shelly Beth Flagel
• 金额: $ 64.6万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10715723
• 关键词: Affect; Amygdaloid structure; Animal Model; Area; Arousal; Attention; Attenuated; BRAIN initiative; Behavior; Behavior Control; Calcium; Cell Nucleus; Choices and Control; Code; Cognition; Complex; Cues; Dissociation; Dorsal; Emotions; Environment; Exposure to; Fluorescence; Food; Foundations; Future; Genetic; Goals; Hippocampus; Hypothalamic structure; Image; Incentives; Individual; Individual Differences; Laboratories; Learning; Location; Machine Learning; Modeling; Modernization; Motivation; Neurons; Pathway interactions; Phenotype; Predictive Value; Process; Property; Rattus; Research; Rewards; Stimulus; Structure; Structure of paraventricular nucleus of thalamus; Thalamic structure; Training; Variant; attentional bias; behavioral phenotyping; brain behavior; experience; fighting; genetic approach; incentive salience; individual variation; locus ceruleus structure; maladaptive behavior; midbrain central gray substance; motivated behavior; multidisciplinary; neural; neural circuit; neuromechanism; novel; response; tool

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.

项目概要/摘要 个人使用复杂的流程来做出选择并确定行动的优先顺序，这些流程为 在我们的现代环境中，我们是基于先前经验的奖励和相关刺激。 周围有大量的刺激物，这些刺激物会争夺我们的注意力，并且常常阻碍目标导向 我们环境中的刺激或线索通过巴甫洛夫学习来控制行为，例如 以前预测奖励的中性刺激获得了动机特性，从而 刺激是否转化为有吸引力且理想的激励刺激。 奖励，或者也作为激励刺激，在不同物种之间有所不同。 个体奖励暗示偏见选择和控制行为的程度各不相同。 然而，造成这种个体差异的过程仍有待确定。 研究中，我们将利用老鼠线索驱动行为的自然变化，并采用新的工具来 当大鼠暴露于巴甫洛夫时，识别潜在神经回路的关键组成部分。 条件方法范式，一些被称为“目标跟踪器”，主要将预测价值归因于 与食物相关的离散线索；而其他被称为“信号追踪者”的人也将激励显着性归因于 因此，这种动物模型使我们能够分离促进的神经过程。 预测性学习与激励性学习以及由此产生的行为。 丘脑核（PVT）已成为整合自上而下输入的关键节点 皮层控制中心和自下而上的皮层下唤醒中心，反过来又引导线索驱动 具体来说，PI 实验室的最新研究表明，信号跟踪行为。 当 PVT 的皮层下输入比皮层输入更重要时就会出现。 刺激 PVT 的皮层输入会减弱体征追踪行为，而这种情况据说会发生 通过将控制从自下而上的过程转变为自上而下的过程，PVT 中的神经代码 目标导向或适应不良行为的综合输入和结果仍有待确定 确定并将成为当前提案的重点。 与基于机器学习的“深度表型分析”结合使用来确定神经特征 PVT 可以预测随后的线索激发行为并构成个体差异的基础。 此外，将使用化学遗传学刺激从前边缘皮层到 PVT 的“自上而下”输入 并将评估由此产生的 PVT 神经活动和大脑行为关系。 研究将产生一个管道，未来的研究将依赖它来更深入地探索神经回路 通过环境中的刺激来控制并激发行为。