Bodor Agnes L, Schneider-Mizell Casey M, Zhang Chi, Elabbady Leila, Mallen Alex, Bergeson Andi, Brittain Derrick, Buchanan JoAnn, Bumbarger Daniel J, Dalley Rachel, Gamlin Clare, Joyce Emily, Kapner Daniel, Kinn Sam, Mahalingam Gayathri, Seshamani Sharmishtaa, Suckow Shelby, Takeno Marc, Torres Russel, Yin Wenjing, Bae J Alexander, Castro Manuel A, Dorkenwald Sven, Halageri Akhilesh, Jia Zhen, Jordan Chris, Kemnitz Nico, Lee Kisuk, Li Kai, Lu Ran, Macrina Thomas, Mitchell Eric, Mondal Shanka Subhra, Mu Shang, Nehoran Barak, Popovych Sergiy, Silversmith William, Turner Nicholas L, Yu Szi-Chieh, Wong William, Wu Jingpeng, Celii Brendan, Campagnola Luke, Seeman Stephanie C, Jarsky Tim, Ren Naixin, Arkhipov Anton, Reimer Jacob, Seung H Sebastian, Reid R Clay, Collman Forrest, da Costa Nuno Maçarico
Allen Institute for Brain Science, Seattle, WA, USA.
Electrical and Computer Engineering Department, Princeton University, Princeton, NJ, USA.
Nat Neurosci. 2025 Jul 28. doi: 10.1038/s41593-025-02004-2.
Despite significant progress in characterizing neocortical cell types, a complete understanding of the synaptic connections of individual excitatory cells remains elusive. This study investigates the connectivity of mouse visual cortex thick tufted layer 5 pyramidal cells, also known as extratelencephalic neurons (L5-ETns), using a 1 mm publicly available electron microscopy dataset. The analysis reveals that, in their immediate vicinity, L5-ETns primarily establish connections with a group of inhibitory cell types, which, in turn, specifically target the L5-ETns back. The most common excitatory targets of L5-ETns are layer 5 intertelencephalic neurons (L5-ITns) and layer 6 (L6) pyramidal cells, whereas synapses with other L5-ETns are less common. When L5-ETns extend their axons to other cortical regions, they tend to connect more with excitatory cells. Our results highlight a circuit motif where a subclass of excitatory cells forms a subcircuit with specific inhibitory cell types. This is achieved using a publicly available, automated approach for synapse recognition and automated cell typing, offering a framework for exploring the connectivity of other neuron types.
尽管在表征新皮质细胞类型方面取得了重大进展，但对单个兴奋性细胞的突触连接的全面理解仍然难以捉摸。本研究使用一个公开可用的1毫米电子显微镜数据集，研究了小鼠视觉皮质厚簇状第5层锥体细胞（也称为脑外神经元，即L5-ETns）的连接性。分析表明，在其紧邻区域，L5-ETns主要与一组抑制性细胞类型建立连接，而这些抑制性细胞类型又特异性地反向靶向L5-ETns。L5-ETns最常见的兴奋性靶点是第5层脑间神经元（L5-ITns）和第6层（L6）锥体细胞，而与其他L5-ETns的突触则较少见。当L5-ETns将其轴突延伸到其他皮质区域时，它们倾向于与兴奋性细胞建立更多连接。我们的结果突出了一种回路模式，即一类兴奋性细胞与特定的抑制性细胞类型形成一个子回路。这是通过一种公开可用的、用于突触识别和自动细胞分型的自动化方法实现的，为探索其他神经元类型的连接性提供了一个框架。
