Basolateral Amygdala Rapid Glutamate Signaling During Reward Decision-Making

奖励决策过程中基底外侧杏仁核快速谷氨酸信号传导

基本信息

批准号：
8482858
负责人：
Kate M Wassum
金额：
$ 32.53万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-01 至 2018-04-30
项目状态：
已结题

项目摘要

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.

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，导致不同奖励的行动之间的决策在很大程度上取决于每个行动结果的预期价值。除此之外，与奖励相关的决策也会受到与奖励配对的环境线索的影响，这样，预测特定奖励的线索就会使人偏向于获得该奖励的行动，即使其他可能更好的选择是可用的。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、眶额皮质和岛叶都受到牵连，但它们如何或是否相互作用来控制决策仍不清楚。从神经化学角度来看，谷氨酸信号传导和神经调节阿片肽也与奖励寻求方面有关，但这些信号与行为的离散方面如何相关尚未阐明。在这里，我们将使用一种新型谷氨酸生物传感器技术，该技术使我们首次能够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，以阐明快速基底外侧杏仁核谷氨酸信号传导在两种情况中的作用：奖励学习和决策。此外，我们将探索控制奖励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大量的人类行为。为此，我们还将探索神经调节阿片肽系统对决策相关基底外侧杏仁核谷氨酸释放的调节。这项研究轨迹的长期目标是表征决策各个方面背后的特定神经化学信号。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，构成由奖励价值驱动的决策以及受环境线索影响的决策。这些形式的决策中的每一种都可能因对毒品、酒精甚至非常美味的食物上瘾而受到干扰。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，以对抗成瘾和强迫性暴饮暴食的这些特定偏差。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，以便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。