Strong and reliable synaptic communication between pyramidal neurons in adult human cerebral cortex

Sarah Hunt; Yoni Leibner; Eline J. Mertens; Natalí Barros-Zulaica; Lida Kanari; Tim S. Heistek; Mahesh M. Karnani; Romy Aardse; René Wilbers; Djai B. Heyer; Natalia A. Goriounova; Matthijs B. Verhoog; Guilherme Testa-Silva; Joshua Obermayer; Tamara Versluis; Ruth Benavides-Piccione; Philip de Witt-Hamer; Sander Idema; David P. Noske; Johannes C. Baayen; Ed S. Lein; Javier DeFelipe; Henry Markram; Huibert D. Mansvelder; Felix Schürmann; Idan Segev; Christiaan P.J. de Kock

doi:10.1093/cercor/bhac246

Strong and reliable synaptic communication between pyramidal neurons in adult human cerebral cortex

Sarah Hunt, Yoni Leibner, Eline J. Mertens, Natalí Barros-Zulaica, Lida Kanari, Tim S. Heistek, Mahesh M. Karnani, Romy Aardse, René Wilbers, Djai B. Heyer, Natalia A. Goriounova, Matthijs B. Verhoog, Guilherme Testa-Silva, Joshua Obermayer, Tamara Versluis, Ruth Benavides-Piccione, Philip de Witt-Hamer, Sander Idema, David P. Noske, Johannes C. BaayenEd S. Lein, Javier DeFelipe, Henry Markram, Huibert D. Mansvelder, Felix Schürmann, Idan Segev, Christiaan P.J. de Kock

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Synaptic transmission constitutes the primary mode of communication between neurons. It is extensively studied in rodent but not human neocortex. We characterized synaptic transmission between pyramidal neurons in layers 2 and 3 using neurosurgically resected human middle temporal gyrus (MTG, Brodmann area 21), which is part of the distributed language circuitry. We find that local connectivity is comparable with mouse layer 2/3 connections in the anatomical homologue (temporal association area), but synaptic connections in human are 3-fold stronger and more reliable (0% vs 25% failure rates, respectively). We developed a theoretical approach to quantify properties of spinous synapses showing that synaptic conductance and voltage change in human dendritic spines are 3-4-folds larger compared with mouse, leading to significant NMDA receptor activation in human unitary connections. This model prediction was validated experimentally by showing that NMDA receptor activation increases the amplitude and prolongs decay of unitary excitatory postsynaptic potentials in human but not in mouse connections. Since NMDA-dependent recurrent excitation facilitates persistent activity (supporting working memory), our data uncovers cortical microcircuit properties in human that may contribute to language processing in MTG.

Original language	English
Pages (from-to)	2857-2878
Number of pages	22
Journal	Cerebral cortex (New York, N.Y. : 1991)
Volume	33
Issue number	6
Early online date	8 Jul 2022
DOIs	https://doi.org/10.1093/cercor/bhac246
Publication status	Published - 15 Mar 2023

Bibliographical note

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].

Funding

This study was supported by funding to the Blue Brain Project, a research center of the Ecole Polytechnique fédérale de Lausanne (EPFL), by support from the Swiss government’s ETH Board of the Swiss Federal Institutes of Technology, by The Spanish “Ministerio de Ciencia e Innovación” (grant PGC2018-094307-B-I00) and by the Center for Neurogenomics and Cognitive Research (Vrije Universiteit Amsterdam Amsterdam). HDM received funding for this work from the US Brain Initiative by the National Institutes of Health under Award Number U01MH114812, the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 945539 (Human Brain Project SGA3), and Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) Gravitation program BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (NWO: 024.004.012). IS received generous support from the Drahi family foundation, from the European Union’s Horizon Framework Program for Research and Innovation under the Specific Grant Agreement No. 785907 (Human Brain Project SGA2), the ETH domain for the Blue Brain Project, the Gatsby Charitable Foundation, and the NIH Grant Agreement U01MH114812.

Funders	Funder number
European Union’s Horizon 2020 Framework Programme for Research and Innovation	945539
European Union’s Horizon Framework Program for Research and Innovation	785907
Swiss Federal Institutes of Technology
National Institutes of Health	U01MH114812
Davis Family Foundation
Gatsby Charitable Foundation
École Polytechnique Fédérale de Lausanne
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	024.004.012
Ministerio de Ciencia e Innovación	PGC2018-094307-B-I00

Keywords

cortex
human brain
L2/L3
NMDA receptor
synaptic transmission

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10.1093/cercor/bhac246

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Hunt, S., Leibner, Y., Mertens, E. J., Barros-Zulaica, N., Kanari, L., Heistek, T. S., Karnani, M. M., Aardse, R., Wilbers, R., Heyer, D. B., Goriounova, N. A., Verhoog, M. B., Testa-Silva, G., Obermayer, J., Versluis, T., Benavides-Piccione, R., de Witt-Hamer, P., Idema, S., Noske, D. P., ... de Kock, C. P. J. (2023). Strong and reliable synaptic communication between pyramidal neurons in adult human cerebral cortex. Cerebral cortex (New York, N.Y. : 1991), 33(6), 2857-2878. https://doi.org/10.1093/cercor/bhac246

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abstract = "Synaptic transmission constitutes the primary mode of communication between neurons. It is extensively studied in rodent but not human neocortex. We characterized synaptic transmission between pyramidal neurons in layers 2 and 3 using neurosurgically resected human middle temporal gyrus (MTG, Brodmann area 21), which is part of the distributed language circuitry. We find that local connectivity is comparable with mouse layer 2/3 connections in the anatomical homologue (temporal association area), but synaptic connections in human are 3-fold stronger and more reliable (0% vs 25% failure rates, respectively). We developed a theoretical approach to quantify properties of spinous synapses showing that synaptic conductance and voltage change in human dendritic spines are 3-4-folds larger compared with mouse, leading to significant NMDA receptor activation in human unitary connections. This model prediction was validated experimentally by showing that NMDA receptor activation increases the amplitude and prolongs decay of unitary excitatory postsynaptic potentials in human but not in mouse connections. Since NMDA-dependent recurrent excitation facilitates persistent activity (supporting working memory), our data uncovers cortical microcircuit properties in human that may contribute to language processing in MTG.",

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Hunt, S, Leibner, Y, Mertens, EJ, Barros-Zulaica, N, Kanari, L, Heistek, TS, Karnani, MM, Aardse, R, Wilbers, R , Heyer, DB , Goriounova, NA, Verhoog, MB, Testa-Silva, G, Obermayer, J, Versluis, T, Benavides-Piccione, R, de Witt-Hamer, P, Idema, S, Noske, DP, Baayen, JC, Lein, ES, DeFelipe, J, Markram, H, Mansvelder, HD, Schürmann, F, Segev, I & de Kock, CPJ 2023, 'Strong and reliable synaptic communication between pyramidal neurons in adult human cerebral cortex', Cerebral cortex (New York, N.Y. : 1991), vol. 33, no. 6, pp. 2857-2878. https://doi.org/10.1093/cercor/bhac246

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AU - Leibner, Yoni

AU - Mertens, Eline J.

AU - Barros-Zulaica, Natalí

AU - Kanari, Lida

AU - Heistek, Tim S.

AU - Karnani, Mahesh M.

AU - Aardse, Romy

AU - Wilbers, René

AU - Heyer, Djai B.

AU - Goriounova, Natalia A.

AU - Verhoog, Matthijs B.

AU - Testa-Silva, Guilherme

AU - Obermayer, Joshua

AU - Versluis, Tamara

AU - Benavides-Piccione, Ruth

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AU - Idema, Sander

AU - Noske, David P.

AU - Baayen, Johannes C.

AU - Lein, Ed S.

AU - DeFelipe, Javier

AU - Markram, Henry

AU - Mansvelder, Huibert D.

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AU - Segev, Idan

AU - de Kock, Christiaan P.J.

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N2 - Synaptic transmission constitutes the primary mode of communication between neurons. It is extensively studied in rodent but not human neocortex. We characterized synaptic transmission between pyramidal neurons in layers 2 and 3 using neurosurgically resected human middle temporal gyrus (MTG, Brodmann area 21), which is part of the distributed language circuitry. We find that local connectivity is comparable with mouse layer 2/3 connections in the anatomical homologue (temporal association area), but synaptic connections in human are 3-fold stronger and more reliable (0% vs 25% failure rates, respectively). We developed a theoretical approach to quantify properties of spinous synapses showing that synaptic conductance and voltage change in human dendritic spines are 3-4-folds larger compared with mouse, leading to significant NMDA receptor activation in human unitary connections. This model prediction was validated experimentally by showing that NMDA receptor activation increases the amplitude and prolongs decay of unitary excitatory postsynaptic potentials in human but not in mouse connections. Since NMDA-dependent recurrent excitation facilitates persistent activity (supporting working memory), our data uncovers cortical microcircuit properties in human that may contribute to language processing in MTG.

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Strong and reliable synaptic communication between pyramidal neurons in adult human cerebral cortex

Abstract

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