Pyramidal neurons (PNs) are covered by thousands of dendritic spines receiving excitatory synaptic inputs. The ultrastructure of dendritic spines shapes signal compartmentalization, but ultrastructural diversity is rarely taken into account in computational models of synaptic integration. Here, we developed a 3D correlative light-electron microscopy (3D-CLEM) approach allowing the analysis of specific populations of synapses in genetically defined neuronal types in intact brain circuits. We used it to reconstruct segments of basal dendrites of layer 2/3 PNs of adult mouse somatosensory cortex and quantify spine ultrastructural diversity. We found that 10% of spines were dually innervated and 38% of inhibitory synapses localized to spines. Using our morphometric data to constrain a model of synaptic signal compartmentalization, we assessed the impact of spinous versus dendritic shaft inhibition. Our results indicate that spinous inhibition is locally more efficient than shaft inhibition and that it can decouple voltage and calcium signaling, potentially impacting synaptic plasticity.

中文翻译：

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3D 相关光学和电子显微镜揭示了体感皮层锥体神经元中双重神经支配的树突棘的独特特性。

锥体神经元 (PN) 被数千个接收兴奋性突触输入的树突棘覆盖。树突棘的超微结构决定了信号区室化，但在突触整合的计算模型中很少考虑超微结构的多样性。在这里，我们开发了一种 3D 相关光电子显微镜 (3D-CLEM) 方法，可以分析完整脑回路中基因定义的神经元类型中的特定突触群体。我们用它来重建成年小鼠体感皮层 2/3 PN 层的基底树突片段并量化脊柱超微结构多样性。我们发现 10% 的棘受到双重神经支配，38% 的抑制性突触位于棘。使用我们的形态测量数据来约束突触信号区室化模型，我们评估了棘与树突轴抑制的影响。我们的结果表明，棘抑制在局部比轴抑制更有效，并且它可以解耦电压和钙信号传导，可能影响突触可塑性。