Hippocampal-orbitofrontal interactions and reward learning

项目摘要（<30行） 海马体和眶额皮质的功能障碍与各种各样的脑损伤有关。 神经精神障碍，包括强迫症、情绪障碍和成瘾。然而，在这方面， 他们的确切贡献尚不清楚。一个主要的问题是大多数关于海马机制的研究 是从啮齿类动物身上提取的然而，海马体的结构发生了巨大的变化 在进化过程中，特别是在那些与精神病理学有关的部分。这需要 灵长类动物模型的使用，但很少有灵长类动物海马体的研究。当前许可 将研究灵长类动物海马体的神经元特性，并确定它如何与 眶额皮质 我们将采用的理论框架来自计算精神病学， 强化学习背后的计算过程如何有助于神经精神病学 疾病我们的假设是海马体和眶额皮质对大脑皮层的活动起着关键作用。 基于模型的强化学习，海马体负责构建认知地图 它实例化任务模型的神经表示，而眶额皮层负责使用 认知地图生成奖励预测，可用于指导决策。为了验证这一 假设，我们将使用高通道计数神经元记录和电刺激的组合， 微刺激 我们将记录海马体中单个神经元在执行基于奖励的学习任务期间的行为 并检查海马神经元是否表现出价值位置调谐。然后我们将研究海马体 可能通过同时从两个结构记录将此信息传达到眶额皮层。 我们的预测是，这种沟通将介导通过同步θ节奏。但这种 措施是相互关联的。建立神经节律的因果关系已经证明是具有挑战性的，因为它是 难以操纵特定的神经元节律而不影响其他神经元节律和/或神经元节律 发射率我们最近开发了一种闭环方法， 并使用这些信号来控制电微刺激的应用。这使我们能够破坏一个 特定频率的神经元节律。我们将使用这种方法来检验是否存在因果关系， theta振荡在基于奖励的学习中。 总之，本建议的结果将提供收敛相关和因果证据的作用 海马和眶额皮层在奖赏学习中的作用及其机制 communicate.这将有助于为未来潜在的额缘神经病治疗方法奠定基础。 基于闭环微刺激的功能障碍。

Project summary (<30 lines) Dysfunction of both the hippocampus and the orbitofrontal cortex have been implicated in a wide variety of neuropsychiatric disorders, including obsessive-compulsive disorder, mood disorders and addiction. However, their exact contribution remains unclear. A major problem is that most research on hippocampal mechanisms is derived from rodent work. However, the structure of the hippocampus has undergone dramatic changes across the course of evolution, particularly in those parts associated with psychopathologies. This necessitates the use of primate models, but there have been few studies of hippocampus in the primate. The current grant will investigate the neuronal properties of hippocampus in the primate and determine how it interacts with orbitofrontal cortex. The theoretical framework that we will employ is derived from computational psychiatry, with a particular focus on how the computational processes underlying reinforcement learning might contribute to neuropsychiatric disease. Our hypothesis is that both hippocampus and orbitofrontal cortex make critical contributions to model-based reinforcement learning, whereby hippocampus is responsible for constructing the cognitive map that instantiates the neural representation of the task model, and orbitofrontal cortex is responsible for using the cognitive map to generate reward predictions that can be used to guide decision-making. To test this hypothesis, we will use a combination of high-channel count neuronal recordings and electrical microstimulation. We will record from single neurons in the hippocampus during performance of a reward-based learning task and examine whether hippocampal neurons show value place tuning. We will then examine how hippocampus might communicate this information to orbitofrontal cortex by recording from both structures simultaneously. Our prediction is that this communication will be mediated via synchronization of theta rhythms. However, such measures are correlative. Establishing a causal role for neural rhythms has proven challenging, since it is difficult to manipulate a specific neuronal rhythm without affecting other neuronal rhythms and/or neuronal firing rates. We have recently developed a closed-loop approach, which involves recording rhythms in real-time and using those signals to control the application of electrical microstimulation. This allows us to disrupt a neuronal rhythm of a specific frequency. We will use this method to examine whether there is a causal role for the theta oscillation in reward-based learning. Taken together, the results of this proposal will provide convergent correlative and causal evidence for the role of hippocampus and orbitofrontal cortex in reward-based learning and the mechanism by which they communicate. This will help lay the groundwork for future potential therapeutic approaches for frontolimbic dysfunction based on closed-loop microstimulation.