Basolateral Amygdala Rapid Glutamate Signaling During Reward Decision-Making

描述(由申请人提供)：在这里，我们试图了解与奖励相关的决策背后的神经化学信号和神经系统。大量证据表明，导致不同回报的行动之间的决定在很大程度上取决于每个行动结果的预期价值。除此之外，与奖励相关的决定也会受到与奖励配对的环境线索的影响，因此预测特定奖励的线索会使人偏向于获得该奖励的行动，即使有其他可能更好的选择。关于奖赏相关决定的回路，许多相互关联的结构，包括基底外侧杏仁核、眶前皮质和脑岛都被牵连， 但他们如何或是否相互作用来控制决策仍不清楚。在神经化学方面，谷氨酸信号和神经调节阿片肽也与奖赏寻求有关，但这些信号如何与行为的不同方面相关尚未阐明。在这里，我们将使用一种新的谷氨酸生物传感器技术，这项技术首次使我们能够监测行为自由的大鼠杏仁基底外侧核细胞外谷氨酸浓度的瞬时变化，以阐明杏仁基底外侧核快速谷氨酸信号在两者中的作用。 奖励学习和决策。此外，我们将探索控制奖赏决定的杏仁核-皮质基底外侧回路。鉴于大脑中信号分子的数量有限，它们之间的相互作用必须发生，才能解释人类的大量行为。为此，我们还将探索神经调节阿片肽系统对杏仁核基底外侧区谷氨酸释放的调节。这一研究轨迹的长期目标是描述构成决策离散方面的特定神经化学信号的特征。重要的是，这项研究旨在识别大脑区域和神经化学系统，这些区域和神经化学系统相互作用，支撑着由奖励价值驱动的决定，以及那些受到环境线索偏见的决定。这些决策的每一种形式都会因为沉迷于毒品、酒精甚至是美味的食物而被打乱。因此，从这一研究轨迹中收集的信息将为开发新的药物疗法提供必要的基础科学，以对抗这些特定的成瘾和强迫性暴食偏差。重要的是，这项拟议的研究利用了一种尚未应用于这些问题的新工具，以提供关于大脑谷氨酸信号在奖赏相关行为中所起作用的新信息。

DESCRIPTION (provided by applicant): Here we seek to understand the neurochemical signals and neurosystems underlying reward-related decision- making. Considerable evidence suggests the decision between actions leading to different rewards relies heavily on the anticipated value of each action's outcome. In addition to this, reward-related decisions are also biased by reward-paired environmental cues, such that a cue predicting a specific reward will bias one towards the action that obtains that reward, even if other, potentially better, options ar available. Regarding the circuitry of reward-related decisions, numerous interconnected structures, including the basolateral amygdala, orbitofrontal cortex and insula are all implicated, but how or if they interact to control decisions remains unclear. Neurochemically, glutamate signaling and neuromodulatory opioid peptides are also implicated in aspects of reward seeking, but how these signals are related to discrete aspects of behavior has not been elucidated. Here we will use a novel glutamate biosensor technology, which allowed us, for the first time, to monitor transient extracellular glutamate concentration changes in the basolateral amygdala of freely-behaving rats, to clarify the role of rapid basolateral amygdala glutamate signaling in both reward learning and decision- making. Moreover, we will explore the basolateral amygdala-cortical circuitry that controls reward-seeking decisions. Given the limited number of signaling molecules in the brain, interactions between them must occur in order to account for the vast number of human behaviors. To this end, we will also explore the regulation of decision-related basolateral amygdala glutamate release by the neuromodulatory opioid peptide systems. The long-term goals of this research trajectory are to characterize the specific neurochemical signals that underlie discrete aspects of decision-making. Importantly, this research aims to identify brain regions and neurochemical systems that interact to underlie decisions driven by reward value as well as those that are biased by environmental cues. Each of these forms of decision-making can be disrupted in addiction to drugs, alcohol or even highly palatable foods. Therefore, information gleaned from this research trajectory will provide the basic science necessary for the development of new pharmacotherapies to combat these specific deviations in addiction and compulsive over-eating. Importantly, the proposed research makes use of a new tool, not yet applied to these questions, in order to provide new information regarding the role of brain glutamate signaling in reward-related behaviors.