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Open Access Publications from the University of California

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

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

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.

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