Regulation of nucleus accumbens reward processing by diverse input signals

通过不同的输入信号调节伏隔核奖励处理

• 批准号: 9977144
• 负责人: Sotiris Masmanidis
• 金额: $ 34.46万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9977144
• 关键词: Abstinence; Address; Amygdaloid structure; Animals; Area; Behavior; Behavioral; Bilateral; Brain; Cocaine; Code; Cues; Discrimination; Dopamine; Drug abuse; Electrophysiology (science); Food; Glutamates; Goals; Hippocampus (Brain); Individual; Learning; Measures; Medial; Mediating; Midbrain structure; Milk; Monitor; Mus; Neurons; Nucleus Accumbens; Pathway interactions; Pattern; Pharmaceutical Preparations; Play; Prefrontal Cortex; Process; Property; Regulation; Rewards; Role; Shapes; Signal Transduction; Source; Stimulus; Structure; Task Performances; Technology; Testing; Training; classical conditioning; conditioning; design; discrete time; dopaminergic neuron; drug of abuse; drug reward; experience; experimental study; glutamatergic signaling; information processing; innovation; learned behavior; neuroregulation; optogenetics; relating to nervous system; reward processing

Project Summary The nucleus accumbens (NAc) plays an important role in the acquisition and expression of many stimulus- reward associations, a process which can be co-opted by drugs of abuse. Information processing in the NAc is thought to be regulated by incoming glutamatergic signals from multiple areas, but the dynamic properties of these different signals are not well understood. This project will focus on the role of three prominent inputs arising from the medial prefrontal cortex, basolateral amygdala, and ventral hippocampus. Studies have begun to reveal the role of these pathways in mediating behavior guided by both natural rewards and drugs of abuse. However, it is still largely unknown to what extent the coordination of NAc neural dynamics with each of those inputs is modulated by experience, dopaminergic signaling, or reward type. The goal of this project is to address these issues using innovative approaches that combine large-scale neural recordings, optogenetics, and reward conditioning in mice. The first aim is to use large-scale neural recordings to determine whether synchrony between the NAc and the three designated inputs is differentially modified during associative reward learning. Additionally, this aim will determine the role of midbrain dopaminergic signaling in input selection, by using transient optogenetic suppression of dopamine neuron activity to modulate synchrony between the NAc and its inputs. The second aim is to combine neural recordings and transient optogenetic suppression of individual input signals to the NAc, to deconstruct the role of specific inputs in shaping neural coding and task performance at different stages of training. The goal in the third aim is to determine how, during periods of reward abstinence, neural synchrony between the NAc and its inputs is differentially modulated by cues previously associated with cocaine or food. Together, this study will greatly advance our understanding of how reward-related information processing in the nucleus accumbens is influenced by signals from three important and functionally diverse input sources.

项目摘要 中脑核（NAc）在许多刺激的获得和表达中起着重要作用， 奖励协会，这一过程可以增选滥用药物。信息处理在NAC是 被认为是由来自多个区域的传入神经元信号调节的，但是 这些不同的信号还没有被很好地理解。本项目将侧重于三项突出投入的作用 源自内侧前额叶皮层、基底外侧杏仁核和腹侧海马体。研究已经开始 揭示这些途径在调节自然奖励和滥用药物引导的行为中的作用。 然而，在很大程度上仍然不清楚NAc神经动力学与这些神经元的协调程度。 输入受经验、多巴胺能信号或奖赏类型的调节。该项目的目标是 使用创新方法解决这些问题，这些方法将联合收割机大规模神经记录，光遗传学， 和奖励条件反射。第一个目标是使用大规模的神经记录来确定是否 NAc和三个指定输入之间的同步在关联奖励期间被差分修改 学习此外，这一目标将确定中脑多巴胺能信号在输入选择中的作用， 使用多巴胺神经元活性的瞬时光遗传学抑制来调节NAc和NAc之间的同步性， 及其输入。第二个目的是将联合收割机神经记录和瞬时光遗传学抑制结合起来， NAc的单个输入信号，以解构特定输入在塑造神经编码和任务中的作用。 在不同训练阶段的表现。第三个目标的目标是确定如何在 奖励禁欲，NAc及其输入之间的神经同步性受到线索的差异调制 以前与可卡因或食物有关。总之，这项研究将大大促进我们对如何理解 伏隔核中与奖励相关的信息处理受到三个重要信号的影响 和功能多样的输入源。