Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations

Tuomo Mäki-Marttunen, Florian Krull, Francesco Bettella, Espen Hagen, Solveig Næss, Torbjørn V. Ness, Torgeir Moberget, Torbjørn Elvsåshagen, Christoph Metzner, Anna Devor, Andrew G. Edwards, Marianne Fyhn, Srdjan Djurovic, Anders M. Dale, Ole A. Andreassen, Gaute T. Einevoll

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Genome-wide association studies have implicated many ion channels in schizophrenia pathophysiology. Although the functions of these channels are relatively well characterized by single-cell studies, the contributions of common variation in these channels to neurophysiological biomarkers and symptoms of schizophrenia remain elusive. Here, using computational modeling, we show that a common biomarker of schizophrenia, namely, an increase in delta-oscillation power, may be a direct consequence of altered expression or kinetics of voltage-gated ion channels or calcium transporters. Our model of a circuit of layer V pyramidal cells highlights multiple types of schizophrenia-related variants that contribute to altered dynamics in the delta-frequency band. Moreover, our model predicts that the same membrane mechanisms that increase the layer V pyramidal cell network gain and response to delta-frequency oscillations may also cause a deficit in a single-cell correlate of the prepulse inhibition, which is a behavioral biomarker highly associated with schizophrenia.

Original languageEnglish (US)
Pages (from-to)875-891
Number of pages17
JournalCerebral Cortex
Volume29
Issue number2
DOIs
StatePublished - Feb 1 2019
Externally publishedYes

Keywords

  • forward modeling of EEG
  • functional genomics
  • ion channels
  • multicompartmental neuron modeling
  • schizophrenia genetics

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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  • Cite this

    Mäki-Marttunen, T., Krull, F., Bettella, F., Hagen, E., Næss, S., Ness, T. V., Moberget, T., Elvsåshagen, T., Metzner, C., Devor, A., Edwards, A. G., Fyhn, M., Djurovic, S., Dale, A. M., Andreassen, O. A., & Einevoll, G. T. (2019). Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations. Cerebral Cortex, 29(2), 875-891. https://doi.org/10.1093/cercor/bhy291