Lui Jan H, Nguyen Nghia D, Grutzner Sophie M, Darmanis Spyros, Peixoto Diogo, Wagner Mark J, Allen William E, Kebschull Justus M, Richman Ethan B, Ren Jing, Newsome William T, Quake Stephen R, Luo Liqun
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; Program in Neuroscience, Harvard University, Boston, MA 02115, USA.
Cell. 2021 Jan 21;184(2):489-506.e26. doi: 10.1016/j.cell.2020.11.046. Epub 2020 Dec 17.
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 Ca 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.
单细胞转录组学已被广泛应用于对哺乳动物大脑中的神经元进行分类，而系统神经科学历来在不考虑细胞类型的情况下分析皮层神经元的编码特性。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靶点，并且大多数靶点接收来自多种类型的投射，但PFC→导水管周围灰质（PAG）除外。通过在自由活动的小鼠的几个二选一任务中，将分子同质的PFC→PAG类型的钙活性与两个异质类进行比较，我们发现所有检测的与任务相关的信号在所有检测的类别中都有定性的呈现。然而，投射到PAG的神经元在提示任务中最有效地编码选择，而投射到对侧PFC的神经元在无提示任务中最有效地编码奖励背景。因此，任务信号以冗余的方式组织，但在具有特定分子解剖特征的细胞之间存在明显的数量偏差。
