Morpho-electric diversity of human hippocampal CA1 pyramidal neurons

Eline J. Mertens; Yoni Leibner; Jean Pie; Anna A. Galakhova; Femke Waleboer; Julia Meijer; Tim S. Heistek; René Wilbers; Djai Heyer; Natalia A. Goriounova; Sander Idema; Matthijs B. Verhoog; Brian E. Kalmbach; Brian R. Lee; Ryder P. Gwinn; Ed S. Lein; Eleonora Aronica; Jonathan Ting; Huibert D. Mansvelder; Idan Segev; Christiaan P.J. de Kock

doi:10.1016/j.celrep.2024.114100

Morpho-electric diversity of human hippocampal CA1 pyramidal neurons

Eline J. Mertens, Yoni Leibner, Jean Pie, Anna A. Galakhova, Femke Waleboer, Julia Meijer, Tim S. Heistek, René Wilbers, Djai Heyer, Natalia A. Goriounova, Sander Idema, Matthijs B. Verhoog, Brian E. Kalmbach, Brian R. Lee, Ryder P. Gwinn, Ed S. Lein, Eleonora Aronica, Jonathan Ting, Huibert D. Mansvelder^*, Idan Segev^*Christiaan P.J. de Kock^*

^*Corresponding author for this work

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

Abstract

Hippocampal pyramidal neuron activity underlies episodic memory and spatial navigation. Although extensively studied in rodents, extremely little is known about human hippocampal pyramidal neurons, even though the human hippocampus underwent strong evolutionary reorganization and shows lower theta rhythm frequencies. To test whether biophysical properties of human Cornu Amonis subfield 1 (CA1) pyramidal neurons can explain observed rhythms, we map the morpho-electric properties of individual CA1 pyramidal neurons in human, non-pathological hippocampal slices from neurosurgery. Human CA1 pyramidal neurons have much larger dendritic trees than mouse CA1 pyramidal neurons, have a large number of oblique dendrites, and resonate at 2.9 Hz, optimally tuned to human theta frequencies. Morphological and biophysical properties suggest cellular diversity along a multidimensional gradient rather than discrete clustering. Across the population, dendritic architecture and a large number of oblique dendrites consistently boost memory capacity in human CA1 pyramidal neurons by an order of magnitude compared to mouse CA1 pyramidal neurons.

Original language	English
Article number	114100
Pages (from-to)	1-16
Number of pages	16
Journal	Cell Reports
Volume	43
Issue number	4
Early online date	11 Apr 2024
DOIs	https://doi.org/10.1016/j.celrep.2024.114100
Publication status	Published - 23 Apr 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

Funding

We thank Sapir Shapira for analysis support. The work was supported by Allen Institute funding and by several grant awards, including awards U01MH114812 and UM1MH130981-01 from the National Institute of Mental Health, grant no. 945539 (Human Brain Project SGA3) from the European Union's Horizon 2020 Framework Programme for Research and Innovation, and the NWO Gravitation program BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (NWO: 024.004.012). N.A.G. is supported by a VI.Vidi.213.014 grant from the Dutch Research Council (NWO). H.D.M. is supported by ERC AdG \u201Cfasthumanneuron\u201D 101093198, and C.P.J.d.K. is supported by an NWO Open Competition grant (ENW-M2, project OCENW.M20.285). I.S. was supported by the Drahi Family Foundation, the ETH domain for the Blue Brain Project, the European Union's Horizon Framework Programme for Research and Innovation under the specific grant agreement no. 785907 (Human Brain Project SGA2), the Gatsby Charitable Foundation, and the NIH grant agreement U01MH114812. This work is dedicated to the memory of Mrs. Lily Safra, a great supporter of brain research. Conceptualization, B.E.K. J.T. E.S.L. H.D.M. I.S. and C.P.J.d.K.; methodology, E.J.M. Y.L. J.P. A.A.G. F.W. T.S.H. and M.B.V.; software, E.J.M. Y.L. J.P. F.W. R.W. D.H. M.B.V. and B.E.K.; investigation, E.J.M. Y.L. J.P. A.A.G. F.W. T.S.H. R.W. D.H. N.A.G. M.B.V. E.A. B.R.L. B.E.K. and J.T.; formal analysis, E.J.M. Y.L. J.P. and J.M.; funding acquisition, B.E.K. B.R.L. E.S.L. J.T. H.D.M. I.S. and C.P.J.d.K.; resources, S.I. and R.P.G.; supervision, H.D.M. I.S. and C.P.J.d.K.; visualization, E.J.M. Y.L. J.P. F.W. H.D.M. and C.P.J.d.K.; writing \u2013 original draft, E.J.M. Y.L. H.D.M. I.S. and C.P.J.d.K.; writing \u2013 review & editing, E.J.M. Y.L. H.D.M. I.S. and C.P.J.d.K. The manuscript was commented on by all authors. The authors declare no competing interests. The work was supported by Allen Institute funding and by several grant awards, including awards U01MH114812 and UM1MH130981-01 from the National Institute of Mental Health , grant no. 945539 (Human Brain Project SGA3) from the European Union\u2019s Horizon 2020 Framework Programme for Research and Innovation, and the NWO Gravitation program BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (NWO: 024.004.012 ). N.A.G. is supported by a VI.Vidi.213.014 grant from the Dutch Research Council ( NWO ). H.D.M. is supported by ERC AdG \u201Cfasthumanneuron\u201D 101093198 , and C.P.J.d.K. is supported by an NWO Open Competition grant (ENW-M2, project OCENW.M20.285). I.S. was supported by the Drahi Family Foundation , the ETH domain for the Blue Brain Project, the European Union\u2019s Horizon Framework Programme for Research and Innovation under the specific grant agreement no. 785907 (Human Brain Project SGA2), the Gatsby Charitable Foundation , and the NIH grant agreement U01MH114812 . This work is dedicated to the memory of Mrs. Lily Safra, a great supporter of brain research.

Funders	Funder number
Gatsby Charitable Foundation
National Institutes of Health
European Union's Horizon 2020 Framework Programme for Research and Innovation
European Union's Horizon Framework Programme for Research and Innovation
Drahi Family Foundation
European Union’s Horizon 2020 Framework Programme for Research and Innovation
Sapir Shapira
European Union’s Horizon Framework Programme for Research and Innovation	785907
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	024.004.012
National Institute of Mental Health	945539
European Research Council	OCENW.M20.285, 101093198
Allen Institute	U01MH114812, UM1MH130981-01

Keywords

adult human hippocampus
CA1
CP: Cell biology
CP: Neuroscience
electrophysiological features
memory capacity
morphology
pyramidal neuron
resection tissue
stratum pyramidale

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10.1016/j.celrep.2024.114100

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Mertens, E. J., Leibner, Y., Pie, J., Galakhova, A. A., Waleboer, F., Meijer, J., Heistek, T. S., Wilbers, R., Heyer, D., Goriounova, N. A., Idema, S., Verhoog, M. B., Kalmbach, B. E., Lee, B. R., Gwinn, R. P., Lein, E. S., Aronica, E., Ting, J., Mansvelder, H. D., ... de Kock, C. P. J. (2024). Morpho-electric diversity of human hippocampal CA1 pyramidal neurons. Cell Reports, 43(4), 1-16. Article 114100. https://doi.org/10.1016/j.celrep.2024.114100

@article{d384d922db0e477eaa7658fac7549960,

title = "Morpho-electric diversity of human hippocampal CA1 pyramidal neurons",

abstract = "Hippocampal pyramidal neuron activity underlies episodic memory and spatial navigation. Although extensively studied in rodents, extremely little is known about human hippocampal pyramidal neurons, even though the human hippocampus underwent strong evolutionary reorganization and shows lower theta rhythm frequencies. To test whether biophysical properties of human Cornu Amonis subfield 1 (CA1) pyramidal neurons can explain observed rhythms, we map the morpho-electric properties of individual CA1 pyramidal neurons in human, non-pathological hippocampal slices from neurosurgery. Human CA1 pyramidal neurons have much larger dendritic trees than mouse CA1 pyramidal neurons, have a large number of oblique dendrites, and resonate at 2.9 Hz, optimally tuned to human theta frequencies. Morphological and biophysical properties suggest cellular diversity along a multidimensional gradient rather than discrete clustering. Across the population, dendritic architecture and a large number of oblique dendrites consistently boost memory capacity in human CA1 pyramidal neurons by an order of magnitude compared to mouse CA1 pyramidal neurons.",

keywords = "adult human hippocampus, CA1, CP: Cell biology, CP: Neuroscience, electrophysiological features, memory capacity, morphology, pyramidal neuron, resection tissue, stratum pyramidale",

author = "Mertens, {Eline J.} and Yoni Leibner and Jean Pie and Galakhova, {Anna A.} and Femke Waleboer and Julia Meijer and Heistek, {Tim S.} and Ren{\'e} Wilbers and Djai Heyer and Goriounova, {Natalia A.} and Sander Idema and Verhoog, {Matthijs B.} and Kalmbach, {Brian E.} and Lee, {Brian R.} and Gwinn, {Ryder P.} and Lein, {Ed S.} and Eleonora Aronica and Jonathan Ting and Mansvelder, {Huibert D.} and Idan Segev and {de Kock}, {Christiaan P.J.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = apr,

day = "23",

doi = "10.1016/j.celrep.2024.114100",

language = "English",

volume = "43",

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Mertens, EJ, Leibner, Y, Pie, J , Galakhova, AA , Waleboer, F, Meijer, J, Heistek, TS , Wilbers, R , Heyer, D , Goriounova, NA, Idema, S, Verhoog, MB, Kalmbach, BE, Lee, BR, Gwinn, RP, Lein, ES, Aronica, E, Ting, J, Mansvelder, HD, Segev, I & de Kock, CPJ 2024, 'Morpho-electric diversity of human hippocampal CA1 pyramidal neurons', Cell Reports, vol. 43, no. 4, 114100, pp. 1-16. https://doi.org/10.1016/j.celrep.2024.114100

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T1 - Morpho-electric diversity of human hippocampal CA1 pyramidal neurons

AU - Mertens, Eline J.

AU - Leibner, Yoni

AU - Pie, Jean

AU - Galakhova, Anna A.

AU - Waleboer, Femke

AU - Meijer, Julia

AU - Heistek, Tim S.

AU - Wilbers, René

AU - Heyer, Djai

AU - Goriounova, Natalia A.

AU - Idema, Sander

AU - Verhoog, Matthijs B.

AU - Kalmbach, Brian E.

AU - Lee, Brian R.

AU - Gwinn, Ryder P.

AU - Lein, Ed S.

AU - Aronica, Eleonora

AU - Ting, Jonathan

AU - Mansvelder, Huibert D.

AU - Segev, Idan

AU - de Kock, Christiaan P.J.

PY - 2024/4/23

Y1 - 2024/4/23

N2 - Hippocampal pyramidal neuron activity underlies episodic memory and spatial navigation. Although extensively studied in rodents, extremely little is known about human hippocampal pyramidal neurons, even though the human hippocampus underwent strong evolutionary reorganization and shows lower theta rhythm frequencies. To test whether biophysical properties of human Cornu Amonis subfield 1 (CA1) pyramidal neurons can explain observed rhythms, we map the morpho-electric properties of individual CA1 pyramidal neurons in human, non-pathological hippocampal slices from neurosurgery. Human CA1 pyramidal neurons have much larger dendritic trees than mouse CA1 pyramidal neurons, have a large number of oblique dendrites, and resonate at 2.9 Hz, optimally tuned to human theta frequencies. Morphological and biophysical properties suggest cellular diversity along a multidimensional gradient rather than discrete clustering. Across the population, dendritic architecture and a large number of oblique dendrites consistently boost memory capacity in human CA1 pyramidal neurons by an order of magnitude compared to mouse CA1 pyramidal neurons.

AB - Hippocampal pyramidal neuron activity underlies episodic memory and spatial navigation. Although extensively studied in rodents, extremely little is known about human hippocampal pyramidal neurons, even though the human hippocampus underwent strong evolutionary reorganization and shows lower theta rhythm frequencies. To test whether biophysical properties of human Cornu Amonis subfield 1 (CA1) pyramidal neurons can explain observed rhythms, we map the morpho-electric properties of individual CA1 pyramidal neurons in human, non-pathological hippocampal slices from neurosurgery. Human CA1 pyramidal neurons have much larger dendritic trees than mouse CA1 pyramidal neurons, have a large number of oblique dendrites, and resonate at 2.9 Hz, optimally tuned to human theta frequencies. Morphological and biophysical properties suggest cellular diversity along a multidimensional gradient rather than discrete clustering. Across the population, dendritic architecture and a large number of oblique dendrites consistently boost memory capacity in human CA1 pyramidal neurons by an order of magnitude compared to mouse CA1 pyramidal neurons.

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KW - CA1

KW - CP: Cell biology

KW - CP: Neuroscience

KW - electrophysiological features

KW - memory capacity

KW - morphology

KW - pyramidal neuron

KW - resection tissue

KW - stratum pyramidale

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M3 - Article

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JO - Cell Reports

JF - Cell Reports

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ER -

Morpho-electric diversity of human hippocampal CA1 pyramidal neurons

Abstract

Bibliographical note

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Keywords

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