Neural circuit mechanisms of affective probabilistic learning

情感概率学习的神经回路机制

• 批准号: 10744542
• 负责人: Peter Rudebeck
• 金额: $ 80.28万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10744542
• 关键词: Affective; Amygdaloid structure; Animal Model; Anxiety Disorders; Area; Attention; Behavior; Behavioral; Cell Nucleus; Communication; Computer Models; Computing Methodologies; Corpus striatum structure; Cues; Data; Environment; Feedback; Genetic; Genetic Models; Goals; Human; Individual; Investigation; Knowledge; Lead; Learning; Limbic System; Link; Macaca; Measures; Memory; Mental Depression; Mental disorders; Monkeys; Mood Disorders; Neural Network Simulation; Neural Pathways; Neurons; Pathologic; Pathway interactions; Pattern; Perception; Prefrontal Cortex; Probability; Process; Punishment; Rewards; Rodent; Role; Signal Transduction; Stimulus; Testing; Time; Update; Work; behavior influence; biomarker identification; cortico-limbic circuits; experimental study; frontal lobe; genetic approach; human model; innovation; insight; neural; neural circuit; neural patterning; neuroimaging; neuromechanism; neurophysiology; neuroregulation; nonhuman primate; psychologic; recurrent neural network; response

Project Summary Pathologically altered affective learning is central to accounts of nearly every psychiatric disorder including depression and anxiety disorders. In humans, non-human primates, and rodents accurately learning which stimuli in our environment predict rewards or punishments is dependent on parts of frontal cortex, striatum, and limbic system, such as amygdala. A considerable amount is known about the neural mechanisms that are associated with adaptive patterns of learning within the circuits connecting these areas. What happens to these patterns of neural activity and the specific pathways involved when learning is enhanced or diminished by psychological processes is much less clear. Obtaining this knowledge is important as it would begin to reveal the specific mechanisms through which learning can be altered, information that is essential for identifying biomarkers in and aiding therapies for individuals with pathologically altered learning. Consequently, our aim here is to begin to establish how bottom-up and top-down processes impact stimulus-reward learning at the level of single neurons and circuit-level interactions. We specifically focus on the ventrolateral prefrontal cortex (PFC) and amygdala as prior work in macaque monkeys has shown that these areas, as opposed to other parts of frontal cortex and striatum, are required for efficient probabilistic stimulus-reward learning. These two areas are also reciprocally connected and, based on neuroimaging investigations functionally interact during learning further suggesting that they form part of a functional circuit essential for stimulus-reward learning. Our hypothesis is that bottom-up and top-down influences on learning impact neural activity within and communication between ventrolateral PFC and the basolateral nucleus of the amygdala but that bottom-up and top-down learning do so through different mechanisms and pathways. We will test our hypothesis by recording activity in ventrolateral PFC and basolateral amygdala as well as interconnected parts of orbital PFC and striatum in macaques learning in a probabilistic stimulus-reward task. We will assess functional interaction between areas using recurrent neural network models and measures of coherence when learning is altered by either bottom-up (aim 1) or top-down (aim 2) processes. To test the causal role of pathways linking amygdala and ventrolateral PFC we will also use chemogenetic approaches to selectively inhibit activity in these circuits. Thus, using an innovative combination of behavioral tasks, neural recordings, chemogenetic neuromodulation, and computational approaches we will establish the patterns of neural activity within and causal importance of PFC-amygdala pathways to bottom-up and top-down influences on learning. Completing these experiments will shed light on the specific neural mechanisms and pathways associated with altered learning, information essential for determining the processes that go awry in psychiatric disorders.

项目概要 病理性改变的情感学习是几乎所有精神疾病的核心，包括 抑郁症和焦虑症。在人类、非人类灵长类动物和啮齿动物中，准确地学习了哪些 我们环境中的刺激预测奖励或惩罚取决于额叶皮层、纹状体和 边缘系统，例如杏仁核。人们对神经机制有相当多的了解 与连接这些区域的回路内的适应性学习模式相关。这些会发生什么 神经活动的模式以及学习通过以下方式增强或减弱时所涉及的特定途径 心理过程还不太清楚。获得这些知识很重要，因为它将开始揭示 可以改变学习的具体机制，对于识别至关重要的信息 学习能力发生病理改变的个体的生物标志物和辅助治疗。因此，我们的目标 这里要开始确定自下而上和自上而下的过程如何影响该级别的刺激奖励学习 单个神经元和电路级相互作用。我们特别关注腹外侧前额皮质 (PFC) 先前在猕猴身上进行的研究表明，这些区域与杏仁核的其他部分不同 额叶皮层和纹状体是有效的概率刺激奖励学习所必需的。这两个区域是 也相互联系，并且基于神经影像学研究，在学习过程中功能性地相互作用 进一步表明它们构成了刺激奖励学习所必需的功能回路的一部分。我们的假设 自下而上和自上而下对学习的影响会影响内部的神经活动和之间的交流 腹外侧 PFC 和杏仁核基底外侧核，但自下而上和自上而下的学习是这样做的 通过不同的机制和途径。我们将通过记录腹外侧的活动来检验我们的假设 猕猴学习中的 PFC 和基底外侧杏仁核以及眼眶 PFC 和纹状体的互连部分 在概率刺激奖励任务中。我们将使用循环神经元评估区域之间的功能相互作用 当学习通过自下而上（目标 1）或自上而下改变时的网络模型和一致性测量 （目标 2）流程。为了测试连接杏仁核和腹外侧 PFC 的通路的因果作用，我们还将使用 化学遗传学方法选择性抑制这些回路的活性。因此，采用创新的组合 行为任务、神经记录、化学遗传学神经调节和计算方法，我们将 自下而上建立 PFC-杏仁核通路内的神经活动模式和因果重要性 以及自上而下对学习的影响。完成这些实验将揭示特定的神经网络 与改变学习相关的机制和途径，确定过程所必需的信息 导致精神疾病。