Regulation of nucleus accumbens reward processing by diverse input signals

项目摘要 伏隔核(NAC)在许多刺激物的获得和表达中起重要作用。 奖励关联，这是一个可以被滥用药物拉拢的过程。NAC中的信息处理是 被认为受来自多个区域的传入谷氨酸能信号的调节，但 这些不同的信号并没有得到很好的理解。该项目将重点关注三个突出的投入的作用 发自内侧前额叶皮质、基底外侧杏仁核和腹侧海马体。研究已经开始 揭示这些通路在调节由自然奖赏和滥用药物引导的行为中的作用。 然而，在很大程度上仍不清楚NAC神经动力学与这些神经动力学的协调程度 输入受到经验、多巴胺能信号或奖赏类型的调节。这个项目的目标是 使用创新方法解决这些问题，这些方法结合了大规模神经记录、光遗传学、 并在小鼠身上进行奖励条件反射。第一个目标是使用大规模神经记录来确定 在关联奖励期间，NAC和三个指定输入之间的同步被不同地修改 学习。此外，这一目标将通过以下方式确定中脑多巴胺能信号在输入选择中的作用 利用对多巴胺神经元活动的瞬时光遗传抑制来调节NAc之间的同步性 以及它的输入。第二个目标是将神经记录和瞬时光遗传抑制相结合 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在 奖赏戒断，NAC及其输入之间的神经同步性受线索的不同调制 以前与可卡因或食物联系在一起。总而言之，这项研究将极大地促进我们对 伏隔核内奖赏相关信息的处理受到来自三个重要脑区的信号的影响 和功能多样化的输入源。

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.