Hippocampal-cortical interactions supporting memory and value-guided decision-making

项目摘要/摘要 以前的经验可以深刻地影响后来的决定。潜在期货的心理模拟 基于对先前行动和结果的记忆是支持自适应的一种策略 决定。大量证据表明，海马体(HC)参与了这一过程：计划 以及基于之前的空间经验来想象未来的事件。更具体地说，HC展示了 时间压缩的神经放电序列，被认为是内部代表预期位置的序列 与动物在环境中的当前位置截然不同。这一“非本地”活动可能会使人们能够考虑 在学习过程中，当最佳选择不清楚时，选择替代路线。为了做出决定， 然而，要走上轨道，大脑不仅必须在内部代表潜在的路径，还必须代表预期的路径 每种选择的价值。前额叶皮质(PFC)的神经活动可以编码选择结果的价值 并受到奖励的调节。这一证据使PFC成为评估 基于奖励历史的潜在空间选择。尽管对各自的功能进行了大量的研究， 无论是内存中的HC或PFC，还是值引导决策，人们对这些电路如何相互作用知之甚少 支持行为。这些回路上的协调神经活动可能有助于在服务于 适应性决策，并可通过学习进行调节。具体地说，这个项目测试了这样一个假设 HC中的非局部表征是空间商议的一种机制，它们是 与PFC值表示协调，以支持奖励历史指导的自适应决策。 验证这一假说需要将通常用于研究HC和空间的方法统一起来 记忆还是PFC和决策。因此，拟议的实验包括同时进行 大鼠变化空间决策任务中HC和PFC的记录 基于神经反馈的奖赏偶发事件(目标1和2)和HC的闭环光学失活 在行为中(目标3)。通过在既定但往往是分开的调查路线的交叉点工作 在记忆和决策方面，拟议的具体目标有可能检验突出的假设和 阐明基于经验的决策过程的神经基础。此外，了解 实现记忆引导决策的神经底物对于理解相关的 HC和PFC回路出现故障的精神障碍，如成瘾、强迫症 精神障碍和精神分裂症。拟议的研究战略得到了一项培训计划的支持，该计划包括 和分析能力，并必须由在技术和概念方面处于领先地位的赞助商指导 项目的方方面面。相应地，研究环境配备了导师、技术和 专业知识，所有这些都在加州大学旧金山分校，这是一个致力于在全球范围内促进健康的合作机构。

Project Summary/Abstract Prior experiences can profoundly shape subsequent decisions. Mental simulation of potential futures based on memories of prior actions and resultant outcomes is one strategy to support making adaptive decisions. Substantial evidence demonstrates that the hippocampus (HC) is involved in this process: planning and imagining future events based on previous spatial experiences. More specifically, the HC exhibits temporally compressed sequences of neural firing that are thought to internally represent prospective locations distinct from the animal’s current place in an environment. This “nonlocal” activity may enable consideration of alternate routes during learning, when the optimal choice is unclear. In order to make a decision about which trajectory to take, however, the brain must not only internally represent potential paths, but also the expected value of each choice. Neural activity in the prefrontal cortex (PFC) can encode the value of a choice’s outcome and is modulated by reward. This evidence makes the PFC a strong candidate site for the evaluation of potential spatial choices based on reward history. Despite substantial research on the respective functions of either the HC or PFC in memory or value-guided decisions, little is known about how these circuits interact to support behavior. Coordinated neural activity across these circuits may facilitate spatial evaluation in service of adaptive decisions and may be modulated by learning. Specifically, this project tests the hypothesis that nonlocal representations in the HC are a mechanism of spatial deliberation, and that they are coordinated with PFC value representations to support reward history-guided adaptive decisions. Testing this hypothesis requires uniting approaches typically used to study either the HC and spatial memory or the PFC and decision-making. The proposed experiments therefore comprise simultaneous recordings of the HC and PFC in rats during the performance of a spatial decision-making task with changing reward contingencies (Aims 1 and 2) and closed-loop optical inactivation of the HC based on neural feedback during behavior (Aim 3). By working at the intersection of established but often separate lines of investigation on memory and decisions, the proposed Specific Aims have the potential to test prominent hypotheses and elucidate the neural underpinnings of experience-based decision processes. Furthermore, understanding the neural substrates that enable memory-guided decision-making is critical to understanding related psychiatric disorders in which HC and PFC circuits malfunction, such as addiction, obsessive-compulsive disorder, and schizophrenia. The proposed research strategy is bolstered by a training plan with experimental and analytical strength and is necessarily guided by a sponsor who is a leader in the technical and conceptual aspects of the project. The research environment is accordingly equipped with mentorship, technology, and expertise, all within UCSF, a collaborative institution dedicated to advancing health worldwide.