Single-cell transcriptomics has been widely applied to classify neurons in the mammalian brain, while systems neuroscience has historically analyzed the encoding properties of cortical neurons without considering cell types. Here we examine how specific transcriptomic types of mouse prefrontal cortex (PFC) projection neurons relate to axonal projections and encoding properties across multiple cognitive tasks. We found that most types projected to multiple targets, and most targets received projections from multiple types, except PFC→PAG (periaqueductal gray). By comparing Ca²⁺ activity of the molecularly homogeneous PFC→PAG type against two heterogeneous classes in several two-alternative choice tasks in freely moving mice, we found that all task-related signals assayed were qualitatively present in all examined classes. However, PAG-projecting neurons most potently encoded choice in cued tasks, whereas contralateral PFC-projecting neurons most potently encoded reward context in an uncued task. Thus, task signals are organized redundantly, but with clear quantitative biases across cells of specific molecular-anatomical characteristics.

单细胞转录组学已广泛应用于对哺乳动物大脑中的神经元进行分类，而系统神经科学历史上一直在不考虑细胞类型的情况下分析皮质神经元的编码特性。在这里，我们研究了小鼠前额叶皮层（PFC）投射神经元的特定转录组类型如何与多个认知任务中的轴突投射和编码特性相关。我们发现大多数类型投射到多个目标，并且大多数目标接收来自多种类型的投射，除了 PFC→PAG（导水管周围灰质）。通过比较分子同质 PFC→PAG 类型与自由活动小鼠的几个二选一选择任务中的两个异质类别的 Ca ²⁺活性，我们发现所分析的所有任务相关信号都定性地存在于所有检查的类别中。然而，PAG 投射神经元在有提示的任务中最有效地编码选择，而对侧 PFC 投射神经元在无提示的任务中最有效地编码奖励上下文。因此，任务信号是冗余组织的，但在具有特定分子解剖特征的细胞之间具有明显的定量偏差。