Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Molecular Brain Science, Division of Developmental Neuroscience, Department of Child Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, and University of Fukui (UGSCD), Osaka University, Suita, Osaka 565-0871, Japan.
Cereb Cortex. 2021 Oct 1;31(11):5225-5238. doi: 10.1093/cercor/bhab153.
Association projections from cortical pyramidal neurons connect disparate intrahemispheric cortical areas, which are implicated in higher cortical functions. The underlying developmental processes of these association projections, especially the initial phase before reaching the target areas, remain unknown. To visualize developing axons of individual neurons with association projections in the mouse neocortex, we devised a sparse labeling method that combined in utero electroporation and confocal imaging of flattened and optically cleared cortices. Using the promoter of an established callosal neuron marker gene that was expressed in over 80% of L2/3 neurons in the primary somatosensory cortex (S1) that project to the primary motor cortex (M1), we found that an association projection of a single neuron was the longest among the interstitial collaterals that branched out in L5 from the earlier-extended callosal projection. Collaterals to M1 elongated primarily within the cortical gray matter with little branching before reaching the target. Our results suggest that dual-projection neurons in S1 make a significant fraction of the association projections to M1, supporting the directed guidance mechanism in long-range corticocortical circuit formation over random projections followed by specific pruning.
从皮质锥体细胞发出的联络投射连接着大脑半球内不同的皮质区域，这些区域与高级皮质功能有关。这些联络投射的潜在发育过程，尤其是在到达靶区之前的初始阶段，目前尚不清楚。为了可视化具有联络投射的单个神经元在小鼠新皮层中的发育轴突，我们设计了一种稀疏标记方法，该方法结合了子宫内电穿孔和扁平化及光透明化皮层的共聚焦成像。我们使用了一个已建立的胼胝体神经元标记基因的启动子，该基因在投射到初级运动皮层（M1）的初级体感皮层（S1）的 L2/3 神经元中表达超过 80%，我们发现，一个神经元的联络投射是从早期扩展的胼胝体投射分支出来的 L5 中间突中的最长投射。M1 的侧支主要在皮质灰质内延伸，在到达靶区之前很少分支。我们的结果表明，S1 中的双投射神经元构成了向 M1 投射的联络投射的重要部分，支持了在随机投射后通过特定修剪形成长程皮质-皮质回路的定向引导机制。
