Structure and function of a neocortical synapse

• Published in: Nature (London) Vol. 591; no. 7848; pp. 111 - 116
• Main Authors: Holler, Simone, Köstinger, German, Martin, Kevan A. C., Schuhknecht, Gregor F. P., Stratford, Ken J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.03.2021; Nature Publishing Group
• Subjects: 101/28; 14/63; 631/378/2597/2600; 631/378/2620/2623; 631/378/3917; 631/378/3920; 631/378/548; 9/74; Animals; Brain; Brain slice preparation; Cell Size; Computational neuroscience; Electron microscopy; Electrophysiological Phenomena; Electrophysiology; High resolution electron microscopy; Humanities and Social Sciences; Light; Light microscopy; Male; Mice; Microscopy; Microscopy, Electron; multidisciplinary; Nematodes; Neocortex - cytology; Neocortex - ultrastructure; Nervous system; Neurons; Neurotransmitter Agents - metabolism; Neurotransmitters; Optical microscopy; Physiology; Pyramidal cells; Pyramidal Cells - cytology; Pyramidal Cells - metabolism; Pyramidal Cells - ultrastructure; Science; Science (multidisciplinary); Somatosensory cortex; Somatosensory Cortex - cytology; Somatosensory Cortex - ultrastructure; Structure-function relationships; Synapses; Synapses - physiology; Synapses - ultrastructure; Synaptic strength; Synaptic Transmission; Wiring
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-020-03134-2

In 1986, electron microscopy was used to reconstruct by hand the entire nervous system of a roundworm, the nematode Caenorhabditis elegans 1 . 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 – 6 , suggesting that they are more complex computational devices than thought, and therefore expanding the computational power of the canonical cortical microcircuitry. Electrophysiology combined with correlated light and electron microscopy confirms the long-standing assumption that the size of a synapse is proportional to its strength, and reveals that neocortical synapses may have greater computational capacity than thought.