In 1986, electron microscopy was used to reconstruct by hand the entire nervous system of a roundworm, the nematode Caenorhabditis elegans¹. Since this landmark study, high-throughput electron-microscopic techniques have enabled reconstructions of much larger mammalian brain circuits at synaptic resolution^2,3. Nevertheless, it remains unknown how the structure of a synapse relates to its physiological transmission strength—a key limitation for inferring brain function from neuronal wiring diagrams. Here we combine slice electrophysiology of synaptically connected pyramidal neurons in the mouse somatosensory cortex with correlated light microscopy and high-resolution electron microscopy of all putative synaptic contacts between the recorded neurons. We find a linear relationship between synapse size and strength, providing the missing link in assigning physiological weights to synapses reconstructed from electron microscopy. Quantal analysis also reveals that synapses contain at least 2.7 neurotransmitter-release sites on average. This challenges existing release models and provides further evidence that neocortical synapses operate with multivesicular release^4,5,6, suggesting that they are more complex computational devices than thought, and therefore expanding the computational power of the canonical cortical microcircuitry.

1986 年，电子显微镜被用于手工重建蛔虫（秀丽隐杆线虫¹线虫）的整个神经系统。自这项具有里程碑意义的研究以来，高通量电子显微镜技术已经能够以突触分辨率重建更大的哺乳动物大脑回路^2,3. 尽管如此，突触的结构与其生理传输强度之间的关系仍然未知——这是从神经元接线图推断大脑功能的一个关键限制。在这里，我们将小鼠体感皮层中突触连接的锥体神经元的切片电生理学与记录神经元之间所有假定突触接触的相关光学显微镜和高分辨率电子显微镜相结合。我们发现突触大小和强度之间存在线性关系，为从电子显微镜重建的突触分配生理权重提供了缺失的环节。量子分析还表明，突触平均至少包含 2.7 个神经递质释放位点。^4,5,6，这表明它们是比想象的更复杂的计算设备，因此扩展了典型皮质微电路的计算能力。