Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, Hubei 430074, China; MoE Key Laboratory for Biomedical Photonics, Collaborative Innovation Center for Biomedical Engineering, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Program in Neuroscience and Medical Scientist Training Program, Stony Brook University, Stony Brook, NY 11790, USA.
Cell Rep. 2019 Mar 12;26(11):3145-3159.e5. doi: 10.1016/j.celrep.2019.02.040.
Parsing diverse nerve cells into biological types is necessary for understanding neural circuit organization. Morphology is an intuitive criterion for neuronal classification and a proxy of connectivity, but morphological diversity and variability often preclude resolving the granularity of neuron types. Combining genetic labeling with high-resolution, large-volume light microscopy, we established a single neuron anatomy platform that resolves, registers, and quantifies complete neuron morphologies in the mouse brain. We discovered that cortical axo-axonic cells (AACs), a cardinal GABAergic interneuron type that controls pyramidal neuron (PyN) spiking at axon initial segments, consist of multiple subtypes distinguished by highly laminar-specific soma position and dendritic and axonal arborization patterns. Whereas the laminar arrangements of AAC dendrites reflect differential recruitment by input streams, the laminar distribution and local geometry of AAC axons enable differential innervation of PyN ensembles. This platform will facilitate genetically targeted, high-resolution, and scalable single neuron anatomy in the mouse brain.
将不同的神经细胞解析为生物类型对于理解神经回路组织是必要的。形态是神经元分类的直观标准，也是连接性的代表，但形态的多样性和可变性常常妨碍解析神经元类型的粒度。我们结合遗传标记和高分辨率、大容量的光显微镜，建立了一个单神经元解剖平台，该平台可以解析、注册和量化小鼠大脑中的完整神经元形态。我们发现，皮层轴突-轴突细胞（AAC）是一种主要的 GABA 能中间神经元类型，它控制着轴突起始段的锥体神经元（PyN）的放电，由多个亚型组成，这些亚型的区别在于具有高度层特异性的胞体位置以及树突和轴突分支模式。AAC 树突的层排列反映了不同输入流的差异招募，而 AAC 轴突的层分布和局部几何形状则可以实现对 PyN 集合的不同神经支配。这个平台将有助于在小鼠大脑中进行基于遗传靶向的高分辨率和可扩展的单神经元解剖。
