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

  • Author(s): Mäki-Marttunen, T
  • Krull, F
  • Bettella, F
  • Hagen, E
  • Næss, S
  • Ness, TV
  • Moberget, T
  • Elvsåshagen, T
  • Metzner, C
  • Devor, A
  • Edwards, AG
  • Fyhn, M
  • Djurovic, S
  • Dale, AM
  • Andreassen, OA
  • Einevoll, GT
  • et al.
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.

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