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

Cereb Cortex. 2019 Feb 1;29(2):875-891. doi: 10.1093/cercor/bhy291.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Delta Rhythm / physiology*
  • Female
  • Genetic Variation / physiology*
  • Humans
  • Male
  • Mice
  • Models, Neurological*
  • Nerve Net / physiology*
  • Schizophrenia / genetics*
  • Schizophrenia / physiopathology*
  • Visual Cortex / physiology
  • Young Adult