Structure and function of axo-axonic inhibition.
Structure and function of axo-axonic inhibition.
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DOI：
10.7554/elife.73783
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发表时间：
2021-12-01
期刊：
影响因子：
7.7
通讯作者：
Costa NMD
中科院分区：
文献类型：
--
作者：
Schneider-Mizell CM;Bodor AL;Collman F;Brittain D;Bleckert A;Dorkenwald S;Turner NL;Macrina T;Lee K;Lu R;Wu J;Zhuang J;Nandi A;Hu B;Buchanan J;Takeno MM;Torres R;Mahalingam G;Bumbarger DJ;Li Y;Chartrand T;Kemnitz N;Silversmith WM;Ih D;Zung J;Zlateski A;Tartavull I;Popovych S;Wong W;Castro M;Jordan CS;Froudarakis E;Becker L;Suckow S;Reimer J;Tolias AS;Anastassiou CA;Seung HS;Reid RC;Costa NMD
哺乳动物皮层中的抑制性神经元表现出不同的生理、形态、分子和连接特征。虽然大量的工作已经测量了几个中间神经元类的平均连接，仍然是一个根本缺乏了解的连接分布的不同抑制性细胞类型与突触分辨率，它如何与靶细胞的属性，以及它如何影响功能。在这里，我们使用大规模电子显微镜和功能成像来解决这些问题的吊灯细胞在2/3层的小鼠视觉皮层。通过电子显微镜的密集重建，我们将完整的吊灯输入映射到153个锥体神经元上。我们发现，突触数量是高度可变的整个人口，并与目标神经元的几个结构特征。轴突-轴突ChC突触数量的这种变异性高于体周抑制中所见的变异性。生物物理模拟表明，所观察到的模式的轴-轴抑制是特别有效的控制兴奋性输出时，兴奋和抑制是共同活跃的。最后，我们使用细胞类型特异性钙成像方法测量了清醒动物中的枝形吊灯细胞活性，并在枝形吊灯细胞中观察到高度相关的活性。在相同的实验中，体内枝形吊灯的群体活动与瞳孔扩张相关，瞳孔扩张是唤醒的代表。总之，这些结果表明枝形吊灯细胞提供了一个电路范围的信号，其强度相对于目标神经元的特性进行了调整。
Inhibitory neurons in mammalian cortex exhibit diverse physiological, morphological, molecular, and connectivity signatures. While considerable work has measured the average connectivity of several interneuron classes, there remains a fundamental lack of understanding of the connectivity distribution of distinct inhibitory cell types with synaptic resolution, how it relates to properties of target cells, and how it affects function. Here, we used large-scale electron microscopy and functional imaging to address these questions for chandelier cells in layer 2/3 of the mouse visual cortex. With dense reconstructions from electron microscopy, we mapped the complete chandelier input onto 153 pyramidal neurons. We found that synapse number is highly variable across the population and is correlated with several structural features of the target neuron. This variability in the number of axo-axonic ChC synapses is higher than the variability seen in perisomatic inhibition. Biophysical simulations show that the observed pattern of axo-axonic inhibition is particularly effective in controlling excitatory output when excitation and inhibition are co-active. Finally, we measured chandelier cell activity in awake animals using a cell-type-specific calcium imaging approach and saw highly correlated activity across chandelier cells. In the same experiments, in vivo chandelier population activity correlated with pupil dilation, a proxy for arousal. Together, these results suggest that chandelier cells provide a circuit-wide signal whose strength is adjusted relative to the properties of target neurons.