- 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
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.