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Structure and function of a neocortical synapse

Author

Listed:
  • Simone Holler

    (University of Zurich and ETH Zurich)

  • German Köstinger

    (University of Zurich and ETH Zurich)

  • Kevan A. C. Martin

    (University of Zurich and ETH Zurich)

  • Gregor F. P. Schuhknecht

    (University of Zurich and ETH Zurich)

  • Ken J. Stratford

    (University of Zurich and ETH Zurich)

Abstract

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 resolution2,3. 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 release4–6, suggesting that they are more complex computational devices than thought, and therefore expanding the computational power of the canonical cortical microcircuitry.

Suggested Citation

  • Simone Holler & German Köstinger & Kevan A. C. Martin & Gregor F. P. Schuhknecht & Ken J. Stratford, 2021. "Structure and function of a neocortical synapse," Nature, Nature, vol. 591(7848), pages 111-116, March.
  • Handle: RePEc:nat:nature:v:591:y:2021:i:7848:d:10.1038_s41586-020-03134-2
    DOI: 10.1038/s41586-020-03134-2
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    Citations

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    Cited by:

    1. Hu, Dongpo & Ma, Linyi & Song, Zigen & Zheng, Zhaowen & Cheng, Lifang & Liu, Ming, 2024. "Multiple bifurcations of a time-delayed coupled FitzHugh–Rinzel neuron system with chemical and electrical couplings," Chaos, Solitons & Fractals, Elsevier, vol. 180(C).
    2. Hang Zhou & Guo-Qiang Bi & Guosong Liu, 2024. "Intracellular magnesium optimizes transmission efficiency and plasticity of hippocampal synapses by reconfiguring their connectivity," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Chad P. Grabner & Daiki Futagi & Jun Shi & Vytas Bindokas & Katsunori Kitano & Eric A. Schwartz & Steven H. DeVries, 2023. "Mechanisms of simultaneous linear and nonlinear computations at the mammalian cone photoreceptor synapse," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Carles Bosch & Tobias Ackels & Alexandra Pacureanu & Yuxin Zhang & Christopher J. Peddie & Manuel Berning & Norman Rzepka & Marie-Christine Zdora & Isabell Whiteley & Malte Storm & Anne Bonnin & Chris, 2022. "Functional and multiscale 3D structural investigation of brain tissue through correlative in vivo physiology, synchrotron microtomography and volume electron microscopy," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. José Moya-Díaz & Ben James & Federico Esposti & Jamie Johnston & Leon Lagnado, 2022. "Diurnal changes in the efficiency of information transmission at a sensory synapse," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Tyler R. Sizemore & Julius Jonaitis & Andrew M. Dacks, 2023. "Heterogeneous receptor expression underlies non-uniform peptidergic modulation of olfaction in Drosophila," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    7. Gregg Wildenberg & Hanyu Li & Vandana Sampathkumar & Anastasia Sorokina & Narayanan Kasthuri, 2023. "Isochronic development of cortical synapses in primates and mice," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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