Human neurons undergo protracted functional maturation into adulthood
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Summary Paragraph Human cognitive development is uniquely prolonged 1–3 , reflecting the extended postnatal maturation of the cerebral cortex where cell-type differentiation 4,5 , synaptogenesis 6,7 , myelination 8 and transcriptional regulation 5,9,10 all follow protracted developmental timelines. However, when the intrinsic physiological properties of human cortical neurons mature, and how this compares with other species, remains unknown. Here we show, through patch-clamp recordings of temporal cortex from an ancestrally diverse cohort spanning infancy to adulthood, that human supragranular pyramidal neurons exhibit pronounced neoteny of their functional properties, maturing well into adult life. In the mouse the same sequence of changes unfolds within weeks and scales tightly with brain volume. In humans this allometric relationship is fundamentally different, with the trajectories of individual properties continuing for decades beyond peak brain volume, up to 7 times more slowly than the difference in brain growth rates alone would predict. Together, these trajectories define a continuous developmental axis along which the neuronal population progresses throughout cognitive development, with the neurons present at each stage differing in how they transform their inputs. Notably, the population diverges only in adolescence, when one of its two adult end-states acquires a distinctive physiology, absent in mice, that characterises the deep supragranular neurons linking distant cortical areas in humans 11,12 and other primates 13–15 . A generative model of the developing human supragranular population, unifying the developmental models of every physiological domain, now captures this protracted maturation from infancy to adulthood, providing a resource for simulation, normative referencing and cross-species age mapping.
Authors 21
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Matthijs B Verhoog corresponding
Affiliation as printed
Division of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town, South Africa
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Affiliation as printed
Division of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town, South Africa
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Affiliation as printed
Division of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town, South Africa
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Affiliation as printed
Division of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town, South Africa
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Affiliation as printed
Division of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town, South Africa
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Affiliation as printed
Division of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town, South Africa
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Affiliation as printed
Division of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town, South Africa
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
Department of Statistics, University of Cape Town, Cape Town, South Africa
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University of Cape Town · Vrije Universiteit Amsterdam
Affiliation as printed
Department of Statistics, University of Cape Town, Cape Town, South Africa
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, The Netherlands
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Affiliation as printed
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, The Netherlands
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Christiaan P. J. de Kock Aachen Department of Systems Neurophysiology Institute of Zoology (Biology 2)
Forschungszentrum Jülich · Jülich Aachen Research Alliance · Vrije Universiteit Amsterdam · RWTH Aachen University
Affiliation as printed
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, The Netherlands
Department of Systems Neurophysiology, Institute of Zoology, RWTH Aachen University, Germany
JARA Brain Institute of Neuroscience and Medicine (INM-10), Forschungszentrum Jülich, Germany
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Forschungszentrum Jülich · Jülich Aachen Research Alliance · Vrije Universiteit Amsterdam · RWTH Aachen University
Affiliation as printed
Department of Systems Neurophysiology, Institute of Zoology, RWTH Aachen University, Germany
JARA Brain Institute of Neuroscience and Medicine (INM-10), Forschungszentrum Jülich, Germany
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, The Netherlands
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Universitätsklinikum Aachen · Vrije Universiteit Amsterdam · RWTH Aachen University
Affiliation as printed
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, The Netherlands
Department of Neurology, Epileptology, Uniklinik RWTH Aachen, Germany
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University of Cape Town · Universitätsklinikum Aachen · Vrije Universiteit Amsterdam · RWTH Aachen University
Affiliation as printed
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, The Netherlands
Department of Neurology, Epileptology, Uniklinik RWTH Aachen, Germany
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Affiliation as printed
Division of Neurosurgery, Department of Surgery, University of Cape Town, Cape Town, South Africa
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Affiliation as printed
Division of Neurosurgery, Department of Surgery, University of Cape Town, Cape Town, South Africa
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Affiliation as printed
Division of Neurosurgery, Department of Surgery, University of Cape Town, Cape Town, South Africa
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
Epilepsy Surgery Unit, Mediclinic Constantiaberg Hospital, Cape Town, South Africa
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Affiliation as printed
Division of Neurosurgery, Department of Surgery, University of Cape Town, Cape Town, South Africa
Epilepsy Surgery Unit, Mediclinic Constantiaberg Hospital, Cape Town, South Africa
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Affiliation as printed
Division of Neurosurgery, Department of Surgery, University of Cape Town, Cape Town, South Africa
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
Epilepsy Surgery Unit, Mediclinic Constantiaberg Hospital, Cape Town, South Africa
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Affiliation as printed
Division of Neurosurgery, Department of Surgery, University of Cape Town, Cape Town, South Africa
Epilepsy Surgery Unit, Mediclinic Constantiaberg Hospital, Cape Town, South Africa
Division of Neurology, Department of Medicine, University of Cape Town, Cape Town, South Africa
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University of Cape Town · Wellcome Centre for Infectious Diseases Research in Africa · Institute of Infectious Disease and Molecular Medicine
Affiliation as printed
Division of Neurology, Department of Medicine, University of Cape Town, Cape Town, South Africa
Epilepsy Surgery Unit, Mediclinic Constantiaberg Hospital, Cape Town, South Africa
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
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University of Cape Town · Wellcome Centre for Infectious Diseases Research in Africa · Institute of Infectious Disease and Molecular Medicine
Affiliation as printed
Division of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town, South Africa
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
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