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

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

Author information

1
Simula Research Laboratory, Oslo, Norway.
2
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
3
Department of Physics, University of Oslo, Oslo, Norway.
4
Faculty of Science and Technology, Norwegian University of Life Sciences, Ås, Norway.
5
Department of Informatics, University of Oslo, Oslo, Norway.
6
Department of Neurology, Oslo University Hospital, Oslo, Norway.
7
Centre for Computer Science and Informatics Research, University of Hertfordshire, Hatfield, UK.
8
Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
9
Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
10
Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
11
Department of Biosciences, University of Oslo, Oslo, Norway.
12
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
13
NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
14
Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

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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