Inter-area communications in a decision-making circuit

项目总结 我们的决定受到近期经验的影响(即历史依赖性)。对…的控制 历史依赖依赖于后顶叶皮质(PPC)。然而，购买力平价也是 许多其他功能，如工作记忆和感觉运动控制。这项建议旨在 阐明PPC电路如何执行多种功能，这是识别 特定PPC故障的原因及处理。我们假设不同的功能 在PPC中涉及不同的子电路，每个子电路具有不同的输入输出连接。我们将对此进行测试 假设，侧重于历史依赖和PPC的两个投射目标的作用， 背侧纹状体(STR)和后次级运动皮质(PM2)。尽管这两个目标 都与历史相关的决定有关，我们的初步结果表明 投射到每个靶点的PPC神经元在很大程度上是不同的，这表明这两条通路 可能有不同的功能。在这里，我们建议采取三种并行的方法来发现 这两条途径中的哪一条调节了历史依赖并表征了长期输入 通向每条路径。首先，我们将比较PPC神经元编码的历史偏差信息 使用双光子钙成像和逆行相结合的方法投射到STR或PM2 对表现出依赖历史的决策偏见的小鼠进行标记。第二，我们将确定 历史相关决策的PPC-STR和PPC-PM2路径的必要性，由 光基因使每条途径失活，并评估其对历史依赖偏倚的影响。 最后，我们将映射特定于两条路径的远程输入 用逆行跨突触狂犬病追踪法研究PPC中历史依赖性偏倚的形成。 总而言之，结果将揭示PPC是否包含专门用于历史的子电路 依赖性以及构成该子电路的输入和输出路径的因素。回答 这些问题将为未来描绘区域间的研究奠定坚实的基础 决策和其他PPC功能的基础电路。此外，对身份的识别 特定功能的通路可能指向神经底物，以进行风险较低的靶向干预 损害其他功能的可能性。

PROJECT SUMMARY Our decisions are influenced by recent experiences (i.e., history dependence). The control of history dependence relies on the posterior parietal cortex (PPC). However, PPC also serves many other functions such as working memory and sensorimotor control. This proposal aims to elucidate how PPC circuits perform multiple functions, a critical step towards identifying the causes and treatments of specific PPC malfunctions. We hypothesize that different functions involve different subcircuits in PPC, each with distinct input-output connectivity. We will test this hypothesis, focusing on the function of history dependence and two projection targets of PPC, the dorsal striatum (STR) and posterior secondary motor cortex (pM2). Although both targets have been implicated for history-dependent decisions, our preliminary results indicate that the PPC neurons projecting to each target are largely distinct, suggesting that the two pathways may have distinct functions. Here we propose to take three parallel approaches to uncover which of the two pathways mediates history dependence and to characterize long-range inputs to each pathway. First, we will compare the history bias information encoded by PPC neurons projecting to STR or pM2, using a combination of two-photon calcium imaging and retrograde labeling in mice exhibiting history-dependent decision bias. Second, we will determine the necessity of PPC-STR and PPC-pM2 pathways for history-dependent decisions, by optogenetically inactivating each pathway and assessing its effect on history-dependent bias. Lastly, we will map long-range inputs specific to the two pathways that contribute to the formation of history-dependent bias in PPC, using retrograde trans-synaptic rabies tracing. Together, the results will reveal whether PPC contains a subcircuit dedicated to history dependence and what constitutes the input and output pathways of that subcircuit. Answers to these questions will lay the solid groundwork for future research that delineates the inter-areal circuits underlying decision-making and other PPC functions. Furthermore, the identification of function-specific pathways may point to neural substrates for targeted intervention with less risk of compromising other functions.