ArticleBiological psychiatry. Cognitive neuroscience and neuroimaging2016
Functional Effects of Schizophrenia-Linked Genetic Variants on Intrinsic Single-Neuron Excitability: A Modeling Study.
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Article in Biological psychiatry. Cognitive neuroscience and neuroimaging, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16citing papers in PubMed
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16 citing papers in PubMed, 27 citations in OpenAlex.
- Genetic mechanisms for impaired synaptic plasticity in schizophrenia revealed by computational modeling.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Single-cell multi-cohort dissection of the schizophrenia transcriptome.Science (New York, N.Y.) · 2024Article
- Agranular frontal cortical microcircuit underlying cognitive control in macaques.Frontiers in neural circuits · 2024Review
- Excitatory and inhibitory effects of HCN channel modulation on excitability of layer V pyramidal cells.PLoS computational biology · 2022Article
- The effect of alterations of schizophrenia-associated genes on gamma band oscillations.Schizophrenia (Heidelberg, Germany) · 2022Article
- Review
- The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia.Scientific reports · 2019Article
- Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations.Cerebral cortex (New York, N.Y. : 1991) · 2019Article
- Computational Modeling of Genetic Contributions to Excitability and Neural Coding in Layer V Pyramidal Cells: Applications to Schizophrenia Pathology.Frontiers in computational neuroscience · 2019Article
- Biophysical Psychiatry-How Computational Neuroscience Can Help to Understand the Complex Mechanisms of Mental Disorders.Frontiers in psychiatry · 2019Review
- A stepwise neuron model fitting procedure designed for recordings with high spatial resolution: Application to layer 5 pyramidal cells.Journal of neuroscience methods · 2018Article
- Pleiotropic effects of schizophrenia-associated genetic variants in neuron firing and cardiac pacemaking revealed by computational modeling.Translational psychiatry · 2017Article
- Genetic tests in major psychiatric disorders-integrating molecular medicine with clinical psychiatry-why is it so difficult?Translational psychiatry · 2017Review
- Genetic evidence for role of integration of fast and slow neurotransmission in schizophrenia.Molecular psychiatry · 2017Review
- Multifactorial Modeling of Impairment of Evoked Gamma Range Oscillations in Schizophrenia.Frontiers in computational neuroscience · 2016Article
- Article
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Authors and funding
10 authors at 1 institution in 2 countries.
Tuomo Mäki-MarttunenNorwegian Centre for Mental Disorders Research and KG Jebsen Centre for Psychosis Research (TM-M, AW, FB, YW, OAA), Institute of Clinical Medicine, University of Oslo, Oslo; and Department of Mathematical Sciences and Technology (GH, GTE), Norwegian University of Life Sciences, Ås, Norway; Departments of Neurosciences (AD, YW, AMD) and Radiology (AD, AMD), University of California, San Diego, La Jolla, California; Martinos Center for Biomedical Imaging (AD), Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and Division of Mental Health and Addiction (FB, YW, OAA) and Department of Medical Genetics (SD), Oslo University Hospital, Oslo; Norwegian Centre for Mental Disorders Research (SD), KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen; and Department of Physics (GTE), University of Oslo, Oslo, Norway.
Geir HalnesNorwegian Centre for Mental Disorders Research and KG Jebsen Centre for Psychosis Research (TM-M, AW, FB, YW, OAA), Institute of Clinical Medicine, University of Oslo, Oslo; and Department of Mathematical Sciences and Technology (GH, GTE), Norwegian University of Life Sciences, Ås, Norway; Departments of Neurosciences (AD, YW, AMD) and Radiology (AD, AMD), University of California, San Diego, La Jolla, California; Martinos Center for Biomedical Imaging (AD), Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and Division of Mental Health and Addiction (FB, YW, OAA) and Department of Medical Genetics (SD), Oslo University Hospital, Oslo; Norwegian Centre for Mental Disorders Research (SD), KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen; and Department of Physics (GTE), University of Oslo, Oslo, Norway.
Anna DevorNorwegian Centre for Mental Disorders Research and KG Jebsen Centre for Psychosis Research (TM-M, AW, FB, YW, OAA), Institute of Clinical Medicine, University of Oslo, Oslo; and Department of Mathematical Sciences and Technology (GH, GTE), Norwegian University of Life Sciences, Ås, Norway; Departments of Neurosciences (AD, YW, AMD) and Radiology (AD, AMD), University of California, San Diego, La Jolla, California; Martinos Center for Biomedical Imaging (AD), Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and Division of Mental Health and Addiction (FB, YW, OAA) and Department of Medical Genetics (SD), Oslo University Hospital, Oslo; Norwegian Centre for Mental Disorders Research (SD), KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen; and Department of Physics (GTE), University of Oslo, Oslo, Norway.
Aree WitoelarNorwegian Centre for Mental Disorders Research and KG Jebsen Centre for Psychosis Research (TM-M, AW, FB, YW, OAA), Institute of Clinical Medicine, University of Oslo, Oslo; and Department of Mathematical Sciences and Technology (GH, GTE), Norwegian University of Life Sciences, Ås, Norway; Departments of Neurosciences (AD, YW, AMD) and Radiology (AD, AMD), University of California, San Diego, La Jolla, California; Martinos Center for Biomedical Imaging (AD), Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and Division of Mental Health and Addiction (FB, YW, OAA) and Department of Medical Genetics (SD), Oslo University Hospital, Oslo; Norwegian Centre for Mental Disorders Research (SD), KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen; and Department of Physics (GTE), University of Oslo, Oslo, Norway.
Francesco BettellaNorwegian Centre for Mental Disorders Research and KG Jebsen Centre for Psychosis Research (TM-M, AW, FB, YW, OAA), Institute of Clinical Medicine, University of Oslo, Oslo; and Department of Mathematical Sciences and Technology (GH, GTE), Norwegian University of Life Sciences, Ås, Norway; Departments of Neurosciences (AD, YW, AMD) and Radiology (AD, AMD), University of California, San Diego, La Jolla, California; Martinos Center for Biomedical Imaging (AD), Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and Division of Mental Health and Addiction (FB, YW, OAA) and Department of Medical Genetics (SD), Oslo University Hospital, Oslo; Norwegian Centre for Mental Disorders Research (SD), KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen; and Department of Physics (GTE), University of Oslo, Oslo, Norway.
Srdjan DjurovicNorwegian Centre for Mental Disorders Research and KG Jebsen Centre for Psychosis Research (TM-M, AW, FB, YW, OAA), Institute of Clinical Medicine, University of Oslo, Oslo; and Department of Mathematical Sciences and Technology (GH, GTE), Norwegian University of Life Sciences, Ås, Norway; Departments of Neurosciences (AD, YW, AMD) and Radiology (AD, AMD), University of California, San Diego, La Jolla, California; Martinos Center for Biomedical Imaging (AD), Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and Division of Mental Health and Addiction (FB, YW, OAA) and Department of Medical Genetics (SD), Oslo University Hospital, Oslo; Norwegian Centre for Mental Disorders Research (SD), KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen; and Department of Physics (GTE), University of Oslo, Oslo, Norway.
Yunpeng WangNorwegian Centre for Mental Disorders Research and KG Jebsen Centre for Psychosis Research (TM-M, AW, FB, YW, OAA), Institute of Clinical Medicine, University of Oslo, Oslo; and Department of Mathematical Sciences and Technology (GH, GTE), Norwegian University of Life Sciences, Ås, Norway; Departments of Neurosciences (AD, YW, AMD) and Radiology (AD, AMD), University of California, San Diego, La Jolla, California; Martinos Center for Biomedical Imaging (AD), Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and Division of Mental Health and Addiction (FB, YW, OAA) and Department of Medical Genetics (SD), Oslo University Hospital, Oslo; Norwegian Centre for Mental Disorders Research (SD), KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen; and Department of Physics (GTE), University of Oslo, Oslo, Norway.
Gaute T EinevollNorwegian Centre for Mental Disorders Research and KG Jebsen Centre for Psychosis Research (TM-M, AW, FB, YW, OAA), Institute of Clinical Medicine, University of Oslo, Oslo; and Department of Mathematical Sciences and Technology (GH, GTE), Norwegian University of Life Sciences, Ås, Norway; Departments of Neurosciences (AD, YW, AMD) and Radiology (AD, AMD), University of California, San Diego, La Jolla, California; Martinos Center for Biomedical Imaging (AD), Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and Division of Mental Health and Addiction (FB, YW, OAA) and Department of Medical Genetics (SD), Oslo University Hospital, Oslo; Norwegian Centre for Mental Disorders Research (SD), KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen; and Department of Physics (GTE), University of Oslo, Oslo, Norway.
Ole A AndreassenNorwegian Centre for Mental Disorders Research and KG Jebsen Centre for Psychosis Research (TM-M, AW, FB, YW, OAA), Institute of Clinical Medicine, University of Oslo, Oslo; and Department of Mathematical Sciences and Technology (GH, GTE), Norwegian University of Life Sciences, Ås, Norway; Departments of Neurosciences (AD, YW, AMD) and Radiology (AD, AMD), University of California, San Diego, La Jolla, California; Martinos Center for Biomedical Imaging (AD), Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and Division of Mental Health and Addiction (FB, YW, OAA) and Department of Medical Genetics (SD), Oslo University Hospital, Oslo; Norwegian Centre for Mental Disorders Research (SD), KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen; and Department of Physics (GTE), University of Oslo, Oslo, Norway.
Anders M DaleNorwegian Centre for Mental Disorders Research and KG Jebsen Centre for Psychosis Research (TM-M, AW, FB, YW, OAA), Institute of Clinical Medicine, University of Oslo, Oslo; and Department of Mathematical Sciences and Technology (GH, GTE), Norwegian University of Life Sciences, Ås, Norway; Departments of Neurosciences (AD, YW, AMD) and Radiology (AD, AMD), University of California, San Diego, La Jolla, California; Martinos Center for Biomedical Imaging (AD), Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and Division of Mental Health and Addiction (FB, YW, OAA) and Department of Medical Genetics (SD), Oslo University Hospital, Oslo; Norwegian Centre for Mental Disorders Research (SD), KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen; and Department of Physics (GTE), University of Oslo, Oslo, Norway.
Oslo University Hospital · NO
Funding
Spatiotemporal Brain Imaging: Microscopic &System LevelR01EB000790 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DALE, ANDERS M · 2002 to 2015
$15.3MNeuronal, glial and BOLD fMRI signals: From BOLD to 2-photon microscopyR01NS057198 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DEVOR, ANNA · 2009 to 2017
$2.6MNIBIB NIH HHS R01 EB000790NINDS NIH HHS R01 NS057198
Abstract
backgroundRecent genome-wide association studies have identified a large number of genetic risk factors for schizophrenia (SCZ) featuring ion channels and calcium transporters. For some of these risk factors, independent prior investigations have examined the effects of genetic alterations on the cellular electrical excitability and calcium homeostasis. In the present proof-of-concept study, we harnessed these experimental results for modeling of computational properties on layer V cortical pyramidal cells and identified possible common alterations in behavior across SCZ-related genes.
methodsWe applied a biophysically detailed multicompartmental model to study the excitability of a layer V pyramidal cell. We reviewed the literature on functional genomics for variants of genes associated with SCZ and used changes in neuron model parameters to represent the effects of these variants.
resultsWe present and apply a framework for examining the effects of subtle single nucleotide polymorphisms in ion channel and calcium transporter-encoding genes on neuron excitability. Our analysis indicates that most of the considered SCZ-related genetic variants affect the spiking behavior and intracellular calcium dynamics resulting from summation of inputs across the dendritic tree.
conclusionsOur results suggest that alteration in the ability of a single neuron to integrate the inputs and scale its excitability may constitute a fundamental mechanistic contributor to mental disease, alongside the previously proposed deficits in synaptic communication and network behavior.
Indexed as
Biophysical modelingFunctional genomicsGenome-wide association studiesLayer V pyramidal cellNeuron excitabilitySchizophrenia
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