Basolateral Amygdala Rapid Glutamate Signaling During Reward Decision-Making

描述（由申请人提供）：在这里，我们试图了解奖励相关决策背后的神经化学信号和神经系统。大量证据表明，在导致不同回报的行动之间做出决定，在很大程度上取决于每个行动结果的预期价值。除此之外，奖励相关的决策也会受到奖励配对环境线索的影响，例如预测特定奖励的线索会使人偏向获得该奖励的行为，即使其他可能更好的选择也是如此。关于奖励相关决策的回路，许多相互关联的结构，包括基底外侧杏仁核，眶额皮质和杏仁核都涉及， 但它们如何或是否相互作用以控制决策仍不清楚。神经化学上，谷氨酸信号和神经调节阿片肽也涉及奖励寻求的方面，但这些信号如何与行为的离散方面相关尚未阐明。在这里，我们将使用一种新的谷氨酸生物传感器技术，这使我们能够第一次监测自由行为大鼠基底外侧杏仁核中短暂的细胞外谷氨酸浓度变化，以阐明基底外侧杏仁核快速谷氨酸信号传导在两个过程中的作用。 奖励学习和决策。此外，我们还将探索控制奖赏寻求决策的基底外侧杏仁核-皮质回路。鉴于大脑中信号分子的数量有限，它们之间必须发生相互作用，才能解释人类大量的行为。为此，我们还将探讨神经调节阿片肽系统对决策相关的基底外侧杏仁核谷氨酸释放的调节。 这项研究的长期目标是描述决策过程中离散方面的特定神经化学信号。重要的是，这项研究旨在确定大脑区域和神经化学系统，这些区域和系统相互作用，以支持由奖励价值驱动的决策，以及那些受环境线索影响的决策。每一种形式的决策都可能在对毒品、酒精甚至非常可口的食物上瘾时被打乱。因此，从这一研究轨迹中收集到的信息将为开发新的药物疗法提供必要的基础科学，以对抗成瘾和强迫性过度饮食的这些特定偏差。重要的是，拟议的研究利用了一种尚未应用于这些问题的新工具，以提供有关大脑谷氨酸信号在奖励相关行为中的作用的新信息。

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.